Inorganic‐Based Aggregation‐Induced Luminescent Materials: Recent Advances and Perspectives

Luminogens with aggregation‐induced emission properties (AIEgens), as a novel and attractive fluorescent molecule, have been used in various fields, such as detection, imaging, and disease treatment, which can overcome the traditional aggregation‐caused quenching of organic fluorescent molecules. Nevertheless, AIEgens still have the problems of water solubility and fluorescence stability in practical applications. Aiming for improving the AIEgens’ performance and promoting the development of diverse applications of AIEgens, it is an available strategy to bind AIEgens to those inorganic materials with abundant variety, easy synthesis, and a unique rigid pore structure. The constructed inorganic‐based AIE materials not only inherit the unique luminescence characteristics of AIEgens, but also retain the biocompatibility and degradability of inorganic materials, endowing AIEgens with more attractive versatility. Herein, the up‐to‐date researches of several representative inorganic‐based AIE materials are introduced, with emphasis on their structure design, synthesis strategy, regulation of fluorescence properties of AIE, and their application in the biological field. Finally, the current situation, challenges, and future development potential of inorganic‐based AIE materials are discussed and prospected.

transition [11] and so on, among which the RIM mechanism proposed by Tang's group is the most widely recognized, including restriction of intramolecular rotation (RIR) and restriction of intramolecular vibration (RIV).
A number of fascinating AIEgens systems have been witnessed over the past few decades, meeting the emission spectra from ultraviolet to near-infrared II.Although these AIEgens have different structures, they are equipped with multiple rotatable or vibrating structural units.Notably, metal nanoclusters (MNCs) have received much attention due to their unique electronic structure and optical properties and also possess AIE properties.Introducing AIEgens into the periphery of ACQ molecules through covalent interactions and converting ACQ molecules into AIE molecules can also enrich the AIEgens library. [12][15][16][17] Unfortunately, there are still the following problems in the practical applications of AIEgens: water dispersibility and fluorescence stability need to be improved; universal construction strategies for AIE materials are lacking to meet different needs.
20][21] Therein, inorganic-based AIE materials have been extensively and intensively investigated, since they inherit the structural characteristics of inorganic materials, with the advantages of controllable morphology and particle size, excellent biocompatibility, easy surface modification, and outstanding water dispersibility, exhibiting distinctive advantages in most cases. [22,23]The surface of inorganic-based AIE materials can be easily modified, usually with hydrophilic groups such as hydroxyl and carboxyl groups, which greatly improve the water dispersibility and stability.More importantly, the rigid matrix or pore structure of the inorganic material can confine AIEgens inside the structure of the material, further enabling AIEgens to aggregate and restrict their intramolecular motion or rotation, thus achieving enhanced fluorescence while improving the fluorescence stability of the material. [24]The combination of inorganic materials as protective agents with MNCs to improve their stability and photoluminescence quantum yield has also been a popular research direction in recent years.Up to date, many efforts in the preparations and applications of inorganic-based AIE materials in different fields have been reported and exhibit very promising potential. [25,26]erein, the state-of-the-art progresses of inorganic-based nanocarriers with porous structures in recent years are summarized, mainly involved in, for example, silicon-based, MOF-based, and other inorganic-materials-based AIE materials, including but not limited to upconversion nanoparticles (UCNPs), layered materials, etc. (Figure 1).More details are further highlighted by discussing basic preparation strategies and new methods of inorganic-based AIE materials, the factors affecting fluorescence and other properties, and the up-to-date biological applications (fluorescence switch detection, bioimaging, and diagnosis and treatment of various diseases).The AIEgens mentioned in this review include organic molecules and MNCs.Finally, this review provides an outlook on the challenges and future development of inorganic-based AIE materials.We expect to provide a new reference idea for the material designs and application prospects of inorganic-based AIE materials.

Silica-Based AIE Materials
Silica nanoparticles have good biocompatibility, adjustable rigid structure, and high colloidal stability. [27,28]There are a large number of silicon hydroxyl groups on the surface of the silica matrix, showing electronegativity, [29,30] which are easy to be modified by functional groups, so that the pure inorganic silica matrix can be chemically activated to meet more biomedical needs.Therefore, silica matrix is considered to be one of the ideal substrates for loading with fluorescent molecules.
The effective integration of silica matrix with AIE active substances and the "AIE functionalization" modification of silica to construct multifunctional nanoplatforms can further expand the application of AIE active substances.Silica plays different roles in composite materials with different structures and variable morphologies, and silica-based AIE nanoplatforms have been widely used in the fields of detection, biological imaging, and disease diagnosis and treatment.

Synthesis and Regulation Strategies of Silica-Based AIE Materials
With further exploration of AIEgens, materials with AIE properties are no longer limited to traditional organic small molecules, which dictate the existence of many different ways of binding AIEgens to silica matrices.In general, there are two types of ways to form nanocomposites by physical or chemical binding of AIEgens to silica matrices: postloading strategy and codoping strategy.

Postloading Strategy
First, silica matrix with the required morphology is prepared by the sol-gel method, Stöber method, and other synthetic patterns, [31] and then AIEgens, such as organic molecules or MNCs, are combined with the silica matrix through noncovalent or covalent interactions to form nanocomposites, which is the basic experimental procedure of post-loading strategy.A relatively simpler synthesis method in the postloading strategy is the physical adsorption.For example, Hou et al. used a concentration diffusion method at room temperature to load 1-(4-Aminophenyl)-1,2,2-triphenylethene (TPE-NH 2 ) into the pore channels of preprepared silica. [32]Since the silica surface usually exhibits negative electrical properties, the AIEgens were stabilized inside the silica by electrostatic interactions.Afterward, the authors coated the nanoparticles with chitosan to prevent AIEgens from leaking.Ma et al. made the surface of mesoporous silica positively charged by amination modification, and the Au nanoclusters (AuNCs) gathered within and on the surface of the silica pores had electrostatic interaction with the silica matrix through stable ligands, which triggered the self-assembly of the composites. [33]lthough the principle of physical adsorption method is simple and easy to operate, it is susceptible to external environmental influences, unstable binding, easy shedding of AIEgens, and thus reducing fluorescence intensity.As well known, the covalent bond formed between small organic molecules AIEgens and silica matrix is more stable than physical adsorption.Wang et al. developed a substitution reaction strategy via covalence of 1-[4-(bromomethyl)phenyl]-1,2,2-triphenylethene and 1,2-bis [4-(bromomethyl)phenyl]-1,2-diphenylethene to the surface of aminated mesoporous silica to form C─N bonds. [34]As shown in Figure 2A,B, the synthesized fluorescent silica showed efficient sensing ability for nitroaromatic explosives and antibiotics.Huang et al. synthesized a fluorescent silane coupling agent (FSCA) through 3-isocyanatopropyltriethoxysilane (IPTS) that reacted with AIE organic small molecules, as shown in Figure 2C. [35]Next, the FSCA was grafted into mesoporous silica by the cocondensation process, and AIEgens-functionalized mesoporous silica was synthesized.Wang and Zhang et al. fixed pyrene derivatives with AIE in silica mesoporous channels through C─N covalent bonds. [36]Wang and Xu et al. used hetero-biofunctional crosslinker reagent N-succinimidyl-3-(2pyridyldithiol)-propionate for amine-sulfhydryl coupling.The AIE fluorescent dye PhENH 2 was grafted onto mesoporous silica nanoparticles to introduce strong fluorescence. [37]

Codoping Strategy
The codoping strategy typically blends AIEgens or silanemodified AIEgens with a silicon source to prepare composite nanoparticles using the "one-pot method."Compared with the postloading strategy, the codoping strategy simplifies the preparation process to a certain extent, and AIEgens are mostly confined to the Si-O crosslinked network, which means that the AIEgens are more firmly bound to the silica matrix and the possibility of blocking the mesoporous silica pores by postloading is eliminated.For example, Pasha et al. mixed platinum-based AIE compounds with cetyltrimethylammonium bromide (CTAB) to confine AIEgens within the micelles, and then tetraethoxysilane (TEOS) was added as a silicon source to construct a fluorescence drug delivery platform. [38]Zhou et al. synthesized a bridged periodic mesoporous silica oxide nanocomposite by a cocondensation process using preprepared silane-modified AIEgens precursor together with TEOS, and CTAB, where AIEgens were restricted in the Si-O crosslinked network (Figure 2D). [39]imilarly, Zhu et al. made use of tetraphenylethylene (TPE)containing triethoxysilane to prepare helical hybrid silica nanofibers, where most of the TPE groups were confined in the pore walls. [40]Besides, Nawaz and coworkers used electrostatic interaction to develop a simple sensitive explosive detection platform by codoping positively charged TPE-based probes with a silicon source through a "one-pot method." [41]n addition, AIEgens and silicone elastomers have important potential in the construction of solid-state emission fluorescence materials.Chen et al. developed a simple and general strategy to construct a multistimulus responsive flexible sensor that emits bright fluorescence. [42]Fluorescent organosilicon films were prepared using the covalent interaction between organosilicon polymer chains and AIEgens to restrict the intramolecular motion of AIEgens.Periodic mesoporous organic silica (PMOs) is an attractive organic-inorganic hybrid material.Using the rigid framework structure and the abundant reaction sites of the pore structure of PMOs, Gao and co-workers embedded the organo-silane precursor (TPE-Si 4 ) with AIE properties into the PMOs matrix by "one-pot method" and constructed a high-performance fluorescent material. [43]However, the limited availability of organo-silane precursors limits the variety of PMOs synthesized.Moreover, the organofunctional groups on the surface of the material are usually directly attached to the silicon atoms, reducing the number of modifiable hydroxyl sites present on the surface, which will affect the water dispersibility of the material and the functionalization of the high concentration of organofunctional groups on the surface. [44,45]If the aforementioned defects can be solved, PMOs-based AIE materials will be a great candidate matrix to combine with AIEgens.
It has been found that amphiphilic AIEgens can be obtained by introducing AIE groups, such as TPE groups, into amphiphilic compounds.These molecules can be used as both light sources and structural guide agents for the synthesis of silica nanocomposites.For example, Zhou et al. designed TPE-based chiral cationic amphiphiles, which can easily self-assemble into helical structures due to molecular interactions such as hydrogen bonds (Figure 2E).Inspired by the self-assembly behaviors, hybrid silica nanoribbons were prepared by a template method, showing AIE and circular polarization luminescence characteristics. [46]Liu et al. presynthesized PEA, an amphiphilic reagent, with AIE activity (Figure 2F), and then PEA self-assembled into fluorescent micelles in solution; after addition of TEOS, the reactants were further hydrolyzed and condensed; finally the fluorescent silica dioxide submicrospheres were obtained, as indicated in Figure 2G. [47]Chang et al. found in their study that the length of alkyl chain in TPE-based amphiphilic AIEgens affects the morphology of the composites. [48]For example, the silica hybrid materials synthesized using AIEgens with shorter alkyl chains tend to form a lamellar structure, while the other tends to form a cubic structure.Yan et al developed a simple and controllable method to prepare the fluorescent silica, during which a TPEfunctionalized carboxylate gemini surfactants and CTAB jointly guide the double-template rule to prepare fluorescent silicon dioxide. [49,50]They found that the TPE-functionalized carboxylate gemini surfactants could both participate in the structural orientation process and provide fluorescence chromophores.
Briefly, AIEgens can be combined with silica matrix through noncovalent or covalent interactions using postloading or codoping strategy.By designing functionalized AIEgens or modified silica substrates, a variety of multifunctional fluorescent nanoplatforms can be constructed to meet the research or application requirements.

Factors Affecting the Luminescent Properties of Silica-Based AIE Materials
AIE is a unique photophysical phenomenon.Since dispersed AIEgens have active intramolecular rotation, energy is dissipated in the form of nonradiative transitions, resulting in no or very weak emission.When the aggregation state is formed, the intramolecular motion is restricted, blocking the nonradiative relaxation channels and opening the radiative decay pathways, in which strong emission is produced. [51]Also, some MNCs have been found to have aggregation-induced enhanced luminescence.In order to maximize the luminescence properties of AIEgens or AIE-active MNCs, it is often necessary to bind with the outer matrix to induce molecular aggregation or provide spatial confinement.Typically, silica has rigid skeleton and variable morphology, [52] and it is easy to form AIE functional composites with high fluorescence efficiency and good photostability by combining different forms of silica with AIE-active substances.Besides, silica as a carrier can be loaded with multiple reagents at the same time to adjust or optimize AIEgens' natural luminescence performance.Therefore, many multifunctional fluorescent nanoplatforms can be designed and constructed to meet the requirements, opening up new possibilities for the application of aggregation-induced luminescent materials.

AIEgens Aggregation Induced by Silica Matrix
Generally, there are three types of methods to induce AIE-active materials aggregation using silica matrix.
First, the fluorescence enhancement is achieved by restricting the intramolecular motion of AIEgens by the domain-limiting effect of the silica pores.For example, Wang et al. synthesized hollow mesoporous silica nanoparticles (HMSNs) using a "surfactants-directed alkaline etching method." [53]Compared with the control group, only AIEgens-functionalized mesoporous silica composites emitted strong blue fluorescence at 487 nm, suggesting that the mesoporous silica matrix plays an important role in enhancing AIEgens' luminescence.Hou et al. prepared mesoporous silica nanoparticles (MSNs) with a pore size of 2.5 nm and a pore volume of 0.62 cm 3 g À1 , and the AIEgens (TPE-CS) were loaded into the pores by postloading strategy. [32]he obtained MSN@TPE-CS showed strong fluorescence emission, indicating that TPE-CS was effectively confined into the mesopores.Huang and co-workers constructed a novel fluorescent silica polymer composite with high fluorescence quantum yield and fluorescence stability via introducing AIEgens into the mesopores of silica through a cationic ring-opening polymerization, which exhibited strong yellow fluorescence in pure water. [54]It has been shown that small nanopores can induce strong emission of AIEgens. [55]But there are few systematic studies on the relationship between the pore size gradient of mesoporous silica and AIEgens luminescence intensity.
Second, the fluorescence could be enhanced by the limiting effect of rigid silica skeleton.The silica matrix has a stable and strong Si-O crosslinked skeleton, which can be used to blend AIEgens with silicon sources in the preparation of silica-based AIE materials, providing a more stable and confined environment for AIEgens.For example, Hao et al. used AIEgens-based organosilane precursors and tetraethyl orthosilicate as mixed silicon sources, confining the groups with AIE activity to Si-O skeleton to prepare organic-inorganic hybrid fluorescent silica nanospheres. [56]Therein, the silica skeleton provided a rigid environment limiting molecular rotation and improved fluorescence emission.Li et al. anchored the TPE groups in the -Si-O-Simolecular networks of solid silica and found that the photoluminescence intensity gradually enhanced with increasing reaction time and increasing size of silica particle. [57]Besides, the emission luminance of MNCs is relatively weak, and it is easy to be affected by the external environment.Fluorescence enhancement can also be achieved by the rational utilization of silica matrix.Zhou et al. synthesized glutathione-capped Au nanoclusters, using silica matrix as a rigid shell. [58]Due to the aggregation-induced enhanced luminescence effect, the rigid structure of silica provides strong anchoring and protection for the MNCs, also reducing the distance between the clusters, thus leading to a substantial increase in fluorescence intensity.Similarly, Ao and co-workers significantly improved the fluorescence emission efficiency and photostability of Cu nanoclusters (CuNCs) by in situ synthesis of silica shells on CuNCs using thiol-containing trialkoxysilane. [59]inally, the surface charge could also be used to induce aggregation to enhance fluorescence emission.Due to the presence of silanol groups, the surface of the silica matrix generally exhibits electronegativity.Based on this property, the silica matrix can be combined with "positively charged cargos."For example, in Song et al.'s study, solid silica was encapsulated with blue fluorescent carbon dots as reference fluorescence. [60]Due to electrostatic interaction, CuNCs further aggregated on the surface of silica nanospheres, showing aggregation-induced enhanced luminescence, and the aggregation states were sensitive to pH.Meanwhile, the surface electrical properties of silica can also be changed by modifying the groups.Similarly, strong fluorescence was found by Wu et al., who prepared a positively charged aminated silica and used the positive charge carried by the silica to attract electronegative AIEgens to gather on the surface of silica. [61]The above method is simple in principle and easy to operate, but it is mostly surface aggregation and the aggregation states of substances are easily affected by the external environment.

Other Factors Affecting the Luminescent Properties
The appearance of AIEgens has overcome the deficiency of aggregation-caused quenching of traditional dyes, and the formation of aggregation states is necessary to achieve excellent fluorescence emission with AIEgens. [62]However, the actual applied environment is diverse and complex.To achieve a satisfactory effect in multiple application scenarios, many attractive silica-based AIE materials have been developed using the passive stimulation of external conditions or addition of various active components in recent years.For example, Hou and co-workers coassembled silica matrixes, superparamagnetic Fe 3 O 4 component, and TPE-functionalized polymers into a multistimulusresponsive fluorescent probe, as shown in Figure 3A. [63]ecause the silica substrates can provide excellent colloidal stability and an easily modified platform, multiple components can be perfectly integrated into one system.TPE groups with AIE activity are bound to the polymer by covalent bonds and remain in a relatively "free" state within the polymer.This means that as external environmental conditions (such as pH and temperature) change, the composites will receive the "stimulus signals," generate aggregation, and respond accurately and sensitively by emitting fluorescence.
Besides "passive stimulation," the active addition of "additives" makes the composites more designable.Kaja et al. prepared Ag/Au plasma nanoparticles coated with silica shells of different thicknesses.Afterward, the AIEgens (NP-4Py) with singlet-oxygen generation ability were aggregated and adsorbed on the surface of core-shell nanoparticles, as shown in Figure 3B. [64]The surface plasmon resonance effects of metal particles are excited by the electromagnetic field, which achieves fluorescence of metal-enhanced AIEgens and formation of metalenhanced singlet oxygen.In addition, the distance between fluorescent molecules and metal nanoparticles is the critical point in the process of metal enhanced fluorescence.As shown in Figure 3C, compared to the control sample without silica shells (NP-4Py þ AgNPs), the fluorescence intensity of AIEgens initially increases significantly with the increase of the thickness of the silica shells.
Furthermore, one of the necessary conditions for the Förster resonance energy transfer (FRET) process to occur is a sufficiently close distance between the donor and the recipient.The excited fluorescent groups transfer energy to the receptor through the dipole, which is a nonradiative process without photon emission or reabsorption.When the fluorescence quantum yield of the recipient is zero, the original fluorescence of the donor is quenched. [65]For instance, Huang et al. took advantage of this mechanism that the UV absorption spectrum of Ag nanoparticles and the emission spectra of fluorescent molecules have obvious overlap to design Ag nanoparticles as a quencher to realize sensitive detection of H 2 O 2 in the form of "fluorescence quenching to turn-on." [66]dditionally, binding chemiluminescent substrates to AIEgens is another way of influencing AIEgens' luminescence.AIEgens can act as energy receptors and become "stimulated objects."As shown in Figure 3D, the chemiluminescent substrates peroxalate (CPPO) and AIEgens (BTPA) were coloaded into the pores of mesoporous silica, and the CPPO could selectively react with H 2 O 2 to produce high-energy intermediates (HEI). [67]The co-loaded BTPA was chemically excited by electron transfer (ET) and back electron transfer (BET) processes between AIEgens and HEI, and finally the H 2 O 2 sensor with high chemiluminescent quantum yield and the low detection limit was developed.In addition, the FRET process can also be ingeniously manipulated to design AIE-based fluorescence nanoplatforms in donor-receptor forms.Moreover, the ratio between emission bands can also be adjusted by tuning the ratio of donors and acceptors in the carriers, which increases the flexibility of the system and expands the available range of fluorescence.By integrating pH-sensitive rhodamine derivatives (RDM) with AIEgens into silica nanoparticles, Zhang et al. developed a FRET probe TR-MP, as shown in Figure 3E. [68]Among them, RDM acted as the receptors and AIEgens as the donors, and the emission bands of AIEgens overlapped well with the absorption bands of RDM.AIEgens accumulated in the silica substrates and produced blue fluorescence emission after excitation.Under acidic conditions, the FRET process can be turned on to excite RDM to emit orange fluorescence, enabling double emission.It can be seen from Figure 3F that the transformation process of fluorescence color and intensity was pH dependent, so the platform could monitor the pH value of lysosomes in a proportional way.Similarly, Yan et al. doped rhodamine-B (RB) into AIEgens-functionalized mesoporous silica matrix by noncovalent action to achieve multicolor emission by adjusting the concentration of RB. [69] It is believed that much more excellent, diverse, and interesting fluorescence systems can be developed in the future by the flexible combination of various chemiluminescent substrates and silica-based aggregation-induced luminescence platforms.

Applications of Silica-Based AIE Materials
Silica-based AIE materials have shown fascinating application prospects in biological fields due to their good biocompatibility and designability.By coloading or postmodifying other biofunctionalized molecules, the silica-based AIE materials have shown great promise in in vitro detection, bioimaging, and diagnostic therapy.

Detection Assays
Ovarian cancer seriously affects women's health.Because the first symptoms are not obvious and the patients' vigilance is reduced, optimal treatment time is missed, and the mortality rate is increased. [70]Therefore, it is of great significance to develop probes for biomarkers of ovarian cancer with lower detection limits and higher sensitivity.Liu and co-workers recently developed biotin-enriched dendritic mesoporous silica nanoparticles (BDMSNs). [71]By covalently coupling AIEgens with BDMSNs, AIEgens were confined to the mesoporous channels to achieve AIE (Figure 4A).In order to increase the concentration of antigen and improve the sensitivity of detection, the authors modified AIEgens and antibodies with biotin, and then used streptavidin to bind probes to multiple antibodies, which greatly increased the enrichment of biotinized antibodies and successfully lowered the limit of detection (LOD).The developed probes were then used in flow immunoassays to simultaneously detect two ovarian cancer biomarkers in human serum, including antigen 125 (CA125) and human epididymal protein 4 (HE4).Different from the above works, Meng et al. adopted a "magnetic bead immunoassay" for sandwich immune detection of HE4. [72]Specially, they doped positively charged AIEgens into silica nanoparticles, then fixed antibodies on the surface of silica nanoparticles, and developed a signal carrier capable of generating strong fluorescence.Antibody-modified magnetic beads are then used as capture probes.Copyright 2021, Elsevier.B) AIEgens accumulate on the surface of a metal core with spacer layers.C) Studies on metal-enhanced AIEgens' fluorescence.Reproduced with permission. [64]Copyright 2022, Elsevier.D) Schematic diagram of the BTPA-PMSN chemiluminescence system.Reproduced with permission. [67]Copyright 2021, American Chemical Society.E) The luminescence principle of biological probe TR-MP and the process of monitoring pH in living cells.F) Dual-emission fluorescence spectrum of TR-MP in buffer solution with pH 3.0-9.0.Reproduced with permission. [68]Copyright 2021, Elsevier.
The above researches take advantage of the fluorescence property of the silica-based aggregation-induced luminescent probes to keep the signal in the state of fluorescence turn-on all the time, and immunoassay is conducted according to the changes of fluorescence signal intensity.However, in order to make probes more adaptable to various scenarios, it is often necessary to develop detection probes that can transition between the fluorescence turn-off and turn-on states.
The interaction between the HIV-I trans-activation responsive (TAR) RNA and the trans-activator of transcription (Tat) protein plays a key role in HIV gene expression in cells. [73]In order to inhibit the binding of TAR RNA and Tat peptide, Li and co-workers proposed a signal amplification strategy when combining AIE and metal-enhanced fluorescence (MEF). [74]A sensitive and reliable nanoplatform (Fe 3 O 4 @Au@Ag@SiO 2 -TAR RNA composite) was constructed for screening and detection of other binding ligands of TAR RNA.As shown in Figure 4B, Fe 3 O 4 is used to achieve the magnetic separation process.In situ-synthesized Au/Ag bimetallic nanoparticles are used to achieve the MEF effect, and silica shells are used to improve the bimetallic stability, providing a thickness of the "isolation layer" and modifiable sites.TAR RNA was covalently bound to the surface of the nanoparticles as a capture probe, and AIEgens labeled Tat peptide as a "reporter" that provided fluorescence signals.At this point, the fluorescence of the "reporter" was in the turn-off state.When the "reporter" interacted specifically with the TAR RNA, the "reporter" was embedded in the large groove of the RNA, which greatly limits the intramolecular motion of AIEgens, leaving the fluorescence in the turn-on state.Moreover, the bimetallic MEF effect further  [71] Copyright 2022, Elsevier.B) HIV-I RNA-binding ligand was screened and detected by the mechanism of metal-enhanced AIEgens' fluorescence.Reproduced with permission. [74]Copyright 2022, American Chemical Society.C) Proportional fluorescent nanoprobe (N-CDs@SiO 2 @BSA-AuNCs) for the detection of glyphosate.Reproduced with permission. [75]Copyright 2023, American Chemical Society.D) Schematic diagram of synthesis process and performance evaluation of red cell membrane camouflaged silicabased AIE materials.Reproduced with permission. [77]Copyright 2022, American Chemical Society.E) Schematic diagram of the preparation process of silica-based AIE composites (Ac-700-DOX-HA) and the strategy of tumor therapy and antibacterial therapy.Reproduced with permission. [81]Copyright 2022, Wiley-VCH GmbH.
amplifies the fluorescence of the "reporter" through a near-field enhancement mechanism.When there are other competitive ligands, the "reporter" is replaced by the displacement process, resulting in a large reduction in fluorescence or even fluorescence turn-off state.Therefore, the changes of fluorescence intensity could be used to evaluate the replacement ability of competitive ligands, and the optimal group was selected for HIV diagnosis and treatment.Very recently, Ma et al. developed a proportional fluorescence sensor. [75]They encased carbon dots in mesoporous silica as reference fluorescence, and AuNCs gathered on the surface of silica through covalent coupling to emit red fluorescence, so that the fluorescence of the probe was in the state of turn-on.The addition of Cu 2þ could quench the red fluorescence of the AuNCs, so that the signal of probes presented a state of turn-off, while the original blue fluorescence remained unchanged.Glyphosate is able to recover red fluorescence by strong chelation with Cu 2þ , thus achieving the turn-onoff-on pattern of fluorescence signals (Figure 4C).Similarly, Cai et al. used MNCs with AIE effect and MnO 2 with fluorescence quenching function to develop enzyme-based biosensors and realized the change of fluorescence turn-off-on-off states under the joint action of various components. [76]

Bioimaging and Disease Treatment
The strong fluorescence properties of silica-based AIE materials give them the ability of visualization with high signal background ratio.Through clever utilization and reasonable regulation of fluorescence signals, they can be used in cell imaging, bacterial imaging, or other biological imaging fields.Dai et al. developed erythrocyte membrane-camouflaged AIE nanoparticles (M@HMSN@P) to assess fetal intestinal maturity by the intensity of the fluorescence signals. [77]As shown in Figure 4D, the authors first synthesized hollow mesoporous silica nanoparticles and encapsulated AIEgens (PyTPA) into mesoporous silica by concentration diffusion method.Afterward, membrane camouflage technology was used to coat the surface of the nanoparticles with a layer of the mouse erythrocyte membrane, so that the nanomaterials can obtain the natural properties of the membrane.The imaging results showed that the nanoparticles were mainly distributed in the intestinal tract and liver of the fetus, and the fluorescence signals were positively correlated with the gestation period, which could be used to evaluate the intestinal maturity and gestational age of the fetus.Liu et al. coloaded AIEgens and antibacterial drugs into biomimetic multispinous mesoporous silica to construct an integrated diagnosis and treatment system. [78]The multiple spines morphology not only increased the loading capacity of fluorescent molecules and antibacterial drugs, but also increased the adhesion to bacteria.More interestingly, as the number of attached bacteria increased, the intramolecular movement of AIEgens was restricted, and the aggregation-induced luminescence mode was turned on, which gradually enhanced the orange fluorescence, enabling real-time bacterial imaging.Besides, He et al. doped Gd 3þ into the mesoporous silica-based AIE materials, which endowed the composites with the ability of magnetic resonance and fluorescence dual-mode imaging. [79]Dineshkumar et al. used conjugated polymers with AIE activity to coassemble with mesoporous silica and further used aptamers to functionalize nanoparticles' surface to develop cell imaging probes that could target cancer cells. [80]ome typical AIEgens can also serve as photosensitizers (PS), which can produce reactive oxygen species (ROS) with strong oxidation capacity under exogenous laser stimulation.There, by coloading PSs AIEgens with drugs or other functionalized molecules into silica carriers, many distinct multifunctional nanoplatforms could be developed.Among them, silica with excellent biocompatibility is not only a tool for AIEgens to aggregate and produce fluorescence, but also is a large-capacity carrier for multifunctional integration.
Recently, Tang's group prepared mesoporous fluorescent silica using amphiphilic AIEgens (MeOTTVP) and CTAB as double templates, which coloaded with antibiotics, anticancer drug doxorubicin (DOX), and the targeted component hyaluronic acid (HA). [81]The restricted MeOTTVP showed large Stokes shift, near-infrared emission characteristics, and efficient ROS generation.Due to the high sensitivity of the obtained composites to the acidic environment, MeOTTVP could be released into tumor cells and targeted to mitochondria by electrostatic interaction to produce ROS under light exposure, showing excellent photodynamic therapeutic properties (Figure 4E).Moreover, they further added Cu 2þ into the above system, endowing the diagnosis and treatment platform with a new function of Cu 2þ -mediated chemodynamic therapy, realizing efficient diagnosis and treatment of cancer. [82]Additionally, Zhang et al. coloaded NO donors, UCNPs, and PSs AIEgens into mesoporous silica to develop a multifunctional anti-inflammatory platform for keratitis treatment. [83]As the light-response core, UCNPs can simultaneously emit ultraviolet light and visible light under 808 nm laser irradiation, which is used to activate NO donors and PSs AIEgens to produce NO and ROS for dual-mode treatment of keratitis.Li et al. combined ultrasmall CuS nanoparticles modified by cyclodextrin with mesoporous silica matrix functionalized by AIEgens to construct a nanoplatform for cell imaging and photothermal treatment of cancer. [84]riefly, the recent progress on silica-based AIE materials is summarized from the perspectives of general synthesis strategies, factors affecting luminescence, and biomedical applications.In terms of the synthesis strategy, postloading strategy and codoping strategy are the mainstream strategies at present.For more functional applications, owing to the richness in species and distinctiveness in property of the existing fluorophores, combining general fluorophores with AIEgens could be attractive and need to be further explored.For example, it is interesting and meaningful to find fluorophores with overlapping absorption emission bands with AIEgens to develop dual-emission or multifunctional fluorescent probes.Besides, some key factors and specific mechanisms affecting fluorescence emission remain unclear and need to be further revealed.The current research mainly focused on in vitro detection, cell imaging, tumor photodynamic therapy, and antibacterial as well as anti-inflammatory aspects.More efforts should pay attention to the material design and its multifunctionalization to seek for a wider range of biomedicine uses, such as real-time monitoring in vivo, integrated diagnosis and treatment of non-tumor diseases, etc.

MOFs-Based AIE Materials
As one of the popular inorganic-organic hybrid framework materials, metal-organic frameworks (MOFs), which consist of a series of metal ion/cluster nodes and organic ligands arranged regularly through coordination, have attracted much attention in recent years. [85]MOFs were first proposed and reported by Yaghi and co-workers in 1995, including Cu-based MOF (Cu(4,4'-bpy) 1.5 •NO 3 (H 2 O) 1.25 ) [86] and Co-based MOF (CoC 6 H 3 (COOH 1/3 ) 3 (NC 5 H 5 ) 2 •2/3NC 5 H 5 ). [87]After that, there has been a rapid explosion of MOFs materials.90] In 1999, Yaghi et al. synthesized the first luminescent MOFs by hydrothermal reaction of rare earth metal ions and terephthalic acid to obtain 3D microporous frameworks M 2 (BDC) 3 •(H 2 O) 4 (M = Eu and Tb) with high stability and luminescence. [91]On this basis, a large number of luminescent MOFs with different structures and properties were successfully prepared by changing the types and modes of action of luminous organic ligands or metal ion/cluster nodes, reaction conditions, and solvent molecules.Its luminescence mechanism which is widely recognized currently includes, but is not limited to, metal-to-ligand charge transfer (MLCT), ligand-to-metal charge transfer (LMCT), guest-introduced emission, and so on. [92]evertheless, there are some shortcomings of conventional luminescent MOFs.Most of the reported luminescent MOFs were constructed with the conjugated planar organic luminescent molecules ligands, such as pyrene, perylene, and other polycyclic aromatic hydrocarbons and their derivatives, while these ligands usually show aggregation-caused quenching (ACQ) effect. [93]In detail, each luminescent MOF particle can be thought as a luminescent cell unit, generally accompanied with nonradiative transition and the decreased fluorescence yield during the synthesis procedure, which shows the trend of the ACQ effect with the increase of concentration. [94]Moreover, lanthanide ions with high quantum yield for luminescent lanthanide-based MOFs (Ln@MOFs) are limited, and the coordination nodes are still unstable in water.As a result, the cleavage of coordination bonds caused by hydrolysis will interrupt the effective ET and reduce the fluorescence. [95,96]Briefly, conventional luminescent MOFs usually exhibit low fluorescence emission, which hinders the development of fascinating practical applications of MOFs in the field of fluorescence.To address the above issues, AIEgens as linkers can be structurally designed and assembled with metal ion/cluster nodes or encapsulated within MOFs into MOF-based AIE materials (AIE@MOFs), which lock AIEgens into the immovable frameworks of MOFs, leading to restricted intramolecular movement or rotation of AIEgens and enhancing the fluorescence emission. [97]MOFs-based AIE materials not only inherit the advantages of aggregation fluorescence emission of AIE and the unique porous structure of MOFs, but also show high fluorescence quantum yield and fluorescence stability, which have attracted more attention in sensing, [98] detection, [99] imaging, [100] tumor therapy, [101] and organic light-emitting diodes (OLEDs). [102]

Synthesis and Regulation Strategies of MOFs-Based AIE Materials
MOFs are porous crystal structures composed of regular repetitive organic ligands and metal nodes.Luminescent MOFs can be constructed by flexible selection of organic ligands, various metal ion/cluster nodes, and regular porous structures. [103]Combining fluorophores with AIE can not only endow MOFs with unique optical properties, but also provide convertible fluorescence signals. [104]Thereinto, AIEgens can act as ligands to coordinate directly with metal nodes, and also be confined to the framework structure; thus, nonradiative transition channel is blocked and fluorescence is enhanced after photoexcitation.Besides, AIEgens can also be regarded as accessory linkers which can be anchored into MOF structures.As metal nodes are part of the construction of MOFs, changes in ion species can affect the way of coordination and ET, thus changing the emission and different physical properties.In addition, AIEgens, as guests, can also be confined to the interior or pores of MOFs by direct one-step encapsulation or physical action, aggregating and emitting light by blocking the intramolecular motion.

Anchoring of AIEgens Organic Ligands in the Frameworks
Organic ligands are the building units for the synthesis of MOFs by bonding with metal nodes and an important component for the construction of MOFs-based AIE materials.The most common approach is to use AIEgens directly as ligands or as accessory linkers anchored to the framework to achieve luminescence properties.AIEgens-based organic units with various structures and functions have been used to design different AIE@MOFs.Among them, AIEgens based on tetraphenylene (TPE) and its derivatives are the most commonly used.By functionalizing TPE, AIEgens can be directly coordinated with metal nodes and fixed to MOFs for a stable and strong fluorescence.
In an earlier study, Dinca et al. designed an AIE@MOFs based on H 4 TCPE as organic ligands and Zn 2þ and Cd 2þ as metal nodes. [105]They found that H 4 TCPE did not emit light in the dissolved state, but showed AIE effect with increasing concentration or the addition of an undesirable solvent due to molecular aggregation.By anchoring H 4 TCPE with Zn 2þ or Cd 2þ , the rotation of benzene rings on AIEgens was restricted, showing the same fluorescence as the previously found aggregation state.They called this phenomenon "matrix coordination-induced emission (MCIE)," which is essentially the same mechanism as the intramolecular motion restriction of AIE.Afterward, Zhu et al. synthesized two types of ZnMOF (ZnTCPE and ZnETTB) by increasing the number of benzene rings and carboxyl groups to prolong AIE rotor ligands on the basis of H 4 TCPE. [106]As shown in Figure 5A, the changes of AIEgens ligands converted the 2D ZnTCPE to 3D ZnETTB.The latter has greater elasticity and pore size (19.16Å), capable of more sensitively sensing N,N-diethylformamide (DEF).The amide-anchored ZnETTB intelligently provided excellent thermal fluorescence and pressure fluorescence response at low pressure.
Usually, AIEgens linkers are aromatic, so the degree of coplanation is able to significantly influence the structure of π-conjugates and optical properties.Compared with terephthalic acid (L0), three AIEgens ligands with similar structures (L1, L2, L3) have been studied and their different emission phenomena have been discovered by Xie et al. (Figure 5B). [107]They found that from L1 to L3, the emission wavelengths in the water/ THF system were 400, 425, 480 nm, and their highest occupied molecular orbital (HOMO)/lowest unoccupied molecular orbital (LUMO) orbit gap (ΔE) are 4.20, 4.00, and 3.67 eV, respectively.L1, L2, and L3 with increasing emission wavelength and decreasing ΔE showed different fluorescence emission and sensitization when combining with lanthanide ion (Ln 3þ ) to form MOFs.This is because the five benzene rings in L1 are noncoplanar and have the smallest degree of conjugation, while the introduction of N atoms in L2 and C═C double bonds in L3 favors the coplane, increasing the degree of conjugation and causing the emission to redshift.Additionally, Dong et al designed three naphthalene butterfly AIEgens and obtained corresponding MOFs (ONP-1, ONP-2, ONP-3) from CuI coordination. [108]The dihedral angles of the naphthalene parts with different orientations changed when combined with CuI, and the geometry and emission of the prepared MOFs changed.
The amount of AIEgens ligands added to MOFs also affects the fluorescence properties of AIE@MOFs.Dong and co-workers designed an AIE@MOF with precise linear regulation of photophysical properties and chemical sensing on a molecular level (NUS-13-x, x is the additive amount of AIEgens ligands). [109]They introduced TPE groups into the 4,4'-terphenyldicarboxylate (H 2 L 1 ) ligands.H 2 L 2 is assembled with Zn 2þ nodes to form NUS-13-x with high porosity, which could reduce the rotation resistance of the TPE groups on the joints (Figure 5C).With the increase of H 2 L 2 ratio in the two ligands, ΔE decreased gradually due to the rigid side of the TPE groups, the maximum emission peaks presented a stepped redshift, and the fluorescence color changed from blue to cyan.The fluorescences of NUS-13-x containing a different number of benzene ring rotors in the ordered frameworks have linear correlation with temperature and viscosity, which can also conduct quantitative analysis of polymer molecular weight in the solution and toxic organic vapors.

Shang et al. constructed FL/CPL MOF with circularly polarized luminescence (CPL) properties by coordinating achiral TPPE
with chiral camphoric acid and Cd 2þ for the first time. [112]ue to the rotation suppression of the TPPE and the deformation of the chiral coordination framework, it was able to respond to external ultrasound and pressure.Additionally, Xie et al obtained a series of AIE-active MOFs (LMOFs) using AIEgens-occurred 2-((2-aminophenylimino) methyl)phenol (APMP) and its derivatives. [113]By changing the substituent types of APMP derivatives, it was found that the electron-drawing groups could redshift the fluorescence, but the electron-donating groups had little effect.
As earlier discussions, several typical AIEgens ligands have been used in the preparation of MOFs.These ligands usually have aromatic groups and bonds (e.g., C = C, C = N bonds) for rotation inhibition and structures for coordination with metal nodes.All in all, by changing the species of AIEgens ligands, it is easy to make unique adjustments to the optical and other properties of AIE@MOFs.

Noncovalent Interaction for Limiting AIEgens to MOFs
Due to the diverse porous structure and simple synthesis of MOFs, AIEgens ligands or molecules can be easily introduced inside the MOFs framework.In addition to AIEgens, nanomaterials or MNCs with AIE property can also be tightly confined to the framework by directly encapsulating into the interior or pores of the MOFs, resulting in high emission.
Physical doping (pore confinement or encapsulation) is an easier synthesis method.As shown in Figure 5D, Wang et al. prepared cube-like Cu-MOF and rod-like Cu-MOF with different mesoporous rates by regulating crystal growth rate and defect engineering, with microporous and mesoporous sizes of 1 and 2.5 nm, respectively. [114]After loading AIEgens respectively by physical adsorption, two kinds of self-luminous PS@Cu-MOF were obtained, and the loading rates (wt%) were both above 50%, while the cube-like Cu-MOF had a slightly higher loading rate, which might indicate that AIEgens could be better matched to its pores.Yang et al. used anion MOF (ZJU-28) to gradually adsorb blue-emitting 2,3,4,5-tetrakis(4-methoxyphenyl)oxazol-3ium (MOTPO) and yellow-emitting 1-methyl -4-(4-(1,2,2triphenylvinyl)pyridin-1-ium (TPEPy) by electrostatic action to obtain MOTPO/TPEPy@ZJU-28. [102]The two AIEgens can be further inhibited by molecular rotation in the pore, contributing to enhanced emission intensity.Unlike general MOFs, γ-cyclodextrin-MOF-K (γ-CD-MOF-K) has holes of different sizes due to its special structure and presence of γ-CD.Qiu et al. directly stirred TPE with γ-CD-MOF-K at room temperature to obtain TPE@γ-CD-MOF-K with a load rate of 16.7%. [115]t should be noted that AIE@MOFs obtained only through physical effects such as pore restriction may be unstable, while the in situ encapsulation of AIEgens during MOF synthesis is a more successful and popular method.AuNCs are MNCs with AIE properties, but exhibit low luminescence efficiency.Cai et al. directly mixed the synthesized AuNCs with Zn 2þ and 2-methylimidazole (2-MI) to obtain AuNCs@ZIF-8.By increasing the dose of encapsulated AuNCs, the fluorescence intensity also gradually increased (4 times that of AuNCs). [116]On this basis, Wei et al. aggregated the dispersed GSH-AuNCs through electrostatic interaction with Zn 2þ in the beginning and mixed with Zn 2þ and 2-MI to form GSH-Au NCs@ZIF-8 in situ (Figure 5E). [117]The fluorescence intensity, lifetime, and stability of AuNCs were greatly improved due to the restriction of ZIF-8 structure and the electrostatic aggregation of Zn 2þ , and the fluorescence intensity only decreased by 12% after 40 days of storage.In addition, microfluidic technology can control details on a microscale, and our group has demonstrated the convenience of this technology. [118,119]Huang et al. used microfluidic technology to input the mixture phase of Zn 2þ and AIEgens (TBP-2) and 2-MI phase, respectively, and directly output ZT MOF with AIE properties.The prepared ZT MOF had controllable sizes, dispersibility, and a stable fluorescence signal. [101]fter encapsulation of the same AIEgens in MOFs with different structures, the resulting AIE@MOFs nanocomposites possess different fluorescence properties.TPE@ZIF-71, TPE@UiO-67, and TPE@MIL-68 (In) were obtained by encapsulating TPE in three kinds of MOFs, respectively. [120]Due to the fact that ZIF-71 was not as hard as UiO-67 and MIL-68 (In) in structure, TPE experienced stronger confinement and exhibited more obvious mechanofluorochromic behavior.

Regulation of Metal Nodes
In MOFs, metal ion/cluster nodes are the units that can coordinate with organic ligands.Felicitous selection and diverse design of nodes play an important role in the luminous performance of AIE@MOFs.Among abundant metal ions, group IIB elements are more suitable as nodes for binding to AIEgens ligands. [121]ecause these metal ions have sufficiently stable d 10 electron configuration with low-orbital energy, they can prevent fluorescence quenching caused by light-induced LMCT.For example, Zn 2þ and TCPE linkers could coordinate to form blue-emitting AIE@MOFs. [122]ery recently, Cai et al. reported the anti-heavy-atom effect of TPE derivatives (DPDPE), which introduced stronger coordination bonds to restrict the intramolecular motion of AIEgens. [123]s shown in Figure 5F, three group IIB metal ions (Zn 2þ , Co 2þ , Hg 2þ ) constructed corresponding AIE@MOFs (Zn-DPDPE, Co-DPDPE, Hg-DPDPE) with AIEgens through coordination.Compared with single DPDPE, the fluorescence emission of Zn-DPDPE had the maximum redshift and produced the largest fluorescence quantum yield, while Co-DPDPE and Hg-DPDPE decreased successively, which may be related to their ionic radii.
Different metal ions have different electron configurations.In order to investigate the optical effects of metal ions with different electron configurations on AIE@MOFs, Wei et al. prepared AMOFs using TCPP as AIEgens linkers and three ions (Cu 2þ , Fe 3þ , and Eu 3þ ) as metal nodes. [124]Among them, the copper ion has the electron configuration of 3d 9 4s 0 .Photoinduced electron transfer (PET) fluorescence quenching occurred due to the TCPP transfer to the unfilled orbital of Cu 2þ .As the reaction time was prolonged, the coordination of MCIE played a leading role, and the fluorescence intensity increased with the emission blueshift.The iron ion with a stable 3d 5 4s 0 electron configuration coordinating with TCPP was able to stabilize the emission wavelength and enhance fluorescence due to the six-coordinated iron atom.The antenna effect of europium ion can be sensitized by TCPP, showing double emission and slight redshift.It is worth noting that, not all metal ion nodes enhance fluorescence emission.As shown in Figure 5G, Zhao and co-workers found that AIE@MOFs synthesized by the coordination of Cu 2þ / Gd 3þ and H 4 ETTC had completely opposite fluorescence phenomena. [125]Compared with stable Gd-ETTC with coordinationrestricted luminescence, LMCT phenomenon occurred in Cu-ETTC under illumination, resulting in reduction of Cu 2þ to Cu þ , which led to fluorescence quenching.The addition of GSH can supply electrons to Cu 2þ , hindering the LMCT process and enhancing the fluorescence emission.
In addition, 3D Mn-based AIE@MOFs were synthesized from Mn 2þ with TIPE and 2,6-NDC. [126]Th 4þ and Bi 3þ were associated with TCBPE to obtain Th-MOF and Bi-MOF respectively, which were highly sensitive to nitro aromatic compounds. [127]f 4þ and H 4 TCBPE was designed as 2D MOF layer and used for enhanced electrochemical fluorescence detection. [128]A combination of Eu/Gd with H 2 TPDB was used to obtain Ln@MOF with gas pressure-dependent fluorescence properties. [97]Ions with different configurations produce different energy transfers and coordination environments from d!d* transitions, resulting in diverse fluorescence performances.Although Ln@MOFs have luminescent properties, the lanthanide ions with high quantum yield are limited (commonly including Eu, Tb, etc.), which require customized and effective sensitizing ligands, while other lanthanide ions (such as La, Lu, Pr, Ho, etc.) have lower quantum yield and are prone to produce nonradiative decay, low probability of electronic transition, and poor adjustability of luminescence peak. [129]Thus there are less articles of Ln@MOFs-based AIE materials published.Through the rational design of AIEgens sensitizing ligands and lanthanide ions, multiemission Ln@MOFs-based AIE materials could be a promising research trend.
Except metal ions as coordination nodes, metal clusters are also used to synthesize AIE@MOFs with larger porosity due to their large size.The most common metal clusters node is the Ag cluster.Wu and co-workers used TPPE-based AIE@MOFs (1⊃DMAC) with bimetallic clusters nodes (Ag8 and Ag12). [130]In contrast to the traditional metal ions nodes, porous structure 1DMAC with larger porosity can more sensitively respond to the objects.Besides, Cd clusters, [131] Pt clusters, [132] Au clusters, [133] Zr clusters, [134] and so on are used as coordination nodes with AIEgens linkers.
Furthermore, inducing the formation of defects in AIE@MOFs can also regulate their intrinsic luminescence properties.Halder et al. reported for the first time the control of fluorescence emission from AIE@MOFs based on defect-based excitation transfer-induced spectral diffusion. [135]The higher the concentration of controlled acid regulator added during synthesis, the higher the defect density, showing dynamic spectral diffusion enhancement and emission spectrum blueshift.The small variation of defect concentration plays an important role in the emission of AIE@MOFs, which provides a new method to explore the diverse properties affecting AIE@MOFs.In brief, there are a variety of options for metal nodes.Dynamic metal coordination bonds have more convenient manipulable controllability and stronger intramolecular interaction, which can regulate the fluorescence properties and pore sizes of AIE@MOFs on a regular basis.

Applications of MOFs-Based AIE Materials
In the past decade, AIE@MOFs nanocomposites with AIEgens as ligands have attracted the interest of an increasing number of scientists.Thanks to the design of crystal structure, adjustable pore size, and various fluorescent emission, AIE@MOFs are given various applications.In this part, the recent developments in these fields will be described.

Detection Assays
Visual fluorescence detection has become a common detection method because of its rapid response, high sensitivity, and specific selectivity. [136]AIE@MOFs are mainly applied in three modes of fluorescence detection, that is, fluorescence turn-off, fluorescence turn-on, and direct quantitative analysis.The realization of these functions depends on the recognition of the guest molecule, metal ion exchange, framework degradation and energy transfer of different species, etc.
The fluorescence turn-off mode is usually through the electron/energy transfer between the fluorescent AIE@MOFs and the guests (e.g., PET, FRET, and competitive absorption of excitation energy) or degradation/exchange of the fluorescent coordination frameworks. [137]For example, Liu et al. used H 4 TCPP as ligand to coordinate with Zr6 clusters to form JLU-MOF60. [99] The synergistic effect of FRET between Cr 2 O 7 2À and JLU-MOF60 and the fluorescence quenching caused by the competitive excitation absorption were used to detect Cr 2 O 7 2À , since Zr-bonding hydroxide has high affinity for Cr 2 O 7 2À .The Zr-MOF synthesized with H 4 BTTB as AIEgens ligand can also detect Cr 2 O 7 2À , with LOD of 0.013 μM. [138]Similarly, the sensitive fluorescence turn-off response to metal ions such as Cu 2þ , Fe 3þ , and Al 3þ was realized based on the above mechanism. [113,139,140]he fluorescence turn-off mode detection can also be achieved by substituting or exchanging AIEgens ligands or metal nodes in AIE@MOFs. [141]Wang and colleagues synthesized AIE-based fluorescent Zn-TCPP. [142]In Figure 6A, due to the stronger coordination ability between Pb 2þ and TCPP, Zn 2þ in the center of Zn-TCPP was replaced by Pb 2þ , which destroyed the structure of MOFs, and AIEgens could perform intramolecular rotation to release energy, thus showing fluorescence quenching.Gao et al. prepared TPE-UIO-66 by anchoring single-dentate TPE ligand (TPE-COOH) on UiO-66 framework. [143]Since HPO 4 2À has a higher affinity for Zr than TPE-COOH, it is able to exchange AIEgens ligands to form P-O-Zr coordination bonds.TPE-COOH replaced by HPO 4 2À dissolved and turned off the fluorescence of TPE-UiO-66.In addition, ratio fluorescence can improve the detection sensitivity.Zhou et al. wrapped blue-emitting AuNCs in red-emitting Eu-MOF in a one-pot method to prepare double-emitting AuNCs@Eu-MOF nanocomplex. [144]The competitive combination of ATP and Eu 3þ could destroy the structure of AuNCs@Eu-MOF, quenching the red fluorescence while the blue fluorescence remained unchanged, achieving the ratio fluorescence detection of ATP.In the same principle, CuNCs-Al@ZIF-90 specifically demonstrated the ratio fluorescence detection of ATP. [145]Releasing intramolecular motion of AIEgens may be another mechanism for fluorescence turn-off, but few studies are available and this may be a topic for future development.
For fluorescence detection using the burst fluorescent AIE@MOFs, the fluorescence turn-off mode with higher LOD is not as specific and sensitive as the fluorescence turn-on mode.AIE@MOFs with fluorescence turn-on mode are initially low emission or no emission.While AIE@MOFs with fluorescence turn-off state can further realize fluorescence turn-on AIE@MOFs with reasonable structural design and introduced objects.This fluorescence turn-on mode can be used to sensitively detect small molecules related to healthy life such as CO 2 , [98] VOCs, [104] and amino acids. [122]Zhu et al. designed emission-free Co-TCPE with AIEgens H 4 TCPE as linkers and Co 2þ as metal nodes and quenchers (Figure 6B). [146]Because of the competitive coordination of nitrogen-rich heterocyclic compounds (NRHCs) and H 4 TCPE, the original Co coordination system disintegrated and TCPE self-aggregation in liquid solution resulted in fluorescence turn-on with fluorescence intensity increasing by 68 times.Very recently, Zhao et al. combined H 4 TCPE and Zn 2þ to obtain water-unstable Zn-TCPE. [147]rom Figure 6C, the structure of Zn-TCPE was partially destroyed in water, so the restricted intramolecular motion was relieved and fluorescence turn-off occurred.When tobramycin (TOB) was added, the coordination with Zn 2þ accelerated the structural destruction of Zn-TCPE, and the free TCPE further self-assembled into the state of AIE.Based on the fluorescence turn-on caused by framework destruction, Zn-TCPE used the same principle to detect small amines through electrostatic interaction and coordination between Zn 2þ and N atoms. [148]dditionally, biomarkers can be detected by fluorescence turnon mode.AuNCs/UiO-66-NH 2 prepared by Tong et al. showed red emission combined with rolling circle amplification (RCA) for the quantitative detection of exosomal pi-RNA by ratio fluorescence. [149]Furthermore, utilizing the porous framework structure of AIE@MOFs, it becomes possible to restrict the aggregation of analytes and generate or enhance their fluorescence. [150,151]eproduced with permission. [142]Copyright 2021, Elsevier.B) Schematic diagram of Co-TCPE fluorescence turn-on for detecting NRHCs.Reproduced with permission. [146]Copyright 2022, American Chemical Society.C) Schematic diagram of Zn-TCPE fluorescence turn-off-on changes in the response process.Reproduced with permission. [147]Copyright 2023, Elsevier.D) Schematic illustration for the synthesis Ab 2 -AuPd@SiO 2 bioconjugate and the fabrication process of the proposed Zr-TCBPE-MOF for ECL immunosensor.Reproduced with permission. [154]Copyright 2022, Wiley-VCH GmbH.E) Schematic diagram of FELISA based on CuNCs-CS@ZIF-8.Reproduced with permission. [156]Copyright 2023, Elsevier.F) Schematic diagram of process of Zn-Py-TPE used for paper-based CL sensor.Reproduced with permission. [157]Copyright 2023, American Chemical Society.
Not only for fluorescence detection, AIE@MOFs have recently been used for electrochemical luminescence (ECL) due to their inherently large specific surface area and enhanced ECL. [128]iong et al. built a multiconvertible ECL resonance energy transfer (ECL-RET) system. [152]The prepared TPE-UiO-66 acted as an energy donor to construct the DNA Y structure by modulating the distance between nanoparticles with different energy receptors (gold and Adriamycin (Dox)).In the presence of tumor biomarker Mucin 1 (MUC1), Dox, which served as an energy receptor for receiving TPE-UiO-66 energy, can be embedded the DNA Y structure to further generate a strong ECL signal on the glass carbon electrode (GCE) loaded with TPE-UiO-66.Co-reactant ECL is also widely concerned because of its low background and high precision.But inefficient ET between molecules may affect the ECL signal.Based on this, Fu et al. developed an in situ coreactant-enhanced ECL AIE@MOFs. [153]Before ECL testing, GCE modified with Zn-tpMOF was incubated with 1,4-Diazabicyclo[2.2.2]octane (DABCO).Due to the short ET path caused by the coordination between DABCO and Zn nodes, it was found that the ECL signal intensity was 49.5 times higher than that of GCE without DABCO.
Enzyme-linked immunosorbent assay (ELISA) is one of the most mature methods for analyzing biological macromolecules.Combining immunoassay based on AIE@MOFs with ECL is a new direction. [154]As shown in Figure 6D, the dumbbell plate-shaped Zr-TCBPE-MOF and neuron-specific enolase (NSE) antibody (Ab 1 ) were coated on the surface of GCE and then combined with the NSE antigens to be tested and the quencher AuPd@SiO 2 -Ab 2 to form a sandwich structure and the obtained quenched ECL immunosensor.Based on the ECL-RET mechanism between Zr-TCBPE-MOF and AuPd@SiO 2 , the quantitative sensitive detection of NSE was realized with a detection limit of 52 fg mL À1 .Moreover, metal nodes exposed on the surface of AIE@MOFs can also directly label antibodies through electrostatic and coordination actions. [155]Furthermore, the combination of fluorescence and immunoassay, namely FELISA, can further expand the application, but there are still some shortcomings, such as high background fluorescence and fluorescence quenching.Combining AIE-property CuNCs with ZIF-8, Zhu et al. constructed a high-throughput fluorescent immunoassay platform for detecting bisphenol S (BPS). [156]As illustrated in Figure 6E, H 2 O 2 can destroy the structure of CuNCs-CS@ZIF-8 and reduce the fluorescence, while Catalase@BPS antibody (CAT@Ab) can consume H 2 O 2 .For the competitive recognition of the antigen and the test product with CAT@Ab, after washing, the fluorescence intensity of the added CuNCs-CS@ZIF-8 was negatively correlated with the concentration of BPS in the test product.This advantage can be leveraged to create a fluorescent lateral flow immunoassay platform that achieves sensitive and rapid point-of-care (POC) detection.Except for the above mentioned, recent studies have developed aggregation-induced chemiluminescence-based AIE@MOFs for portable paper-based detection platforms (Figure 6F). [157]ot only molecules or ions, AIE@MOFs can also actively respond to external environmental stimuli, including but not limited to pressure, temperature, viscosity, magnetic field, etc., which may be the direction of future applications.

Biological Imaging and Tumor Therapy
Unlike the ACQ phenomenon of traditional fluorescent molecules, AIEgens can display fluorescence of different intensity or color depending on the degree of aggregation caused by changes in solubility in the environment.The fluorescence properties of AIEgens not only can be directly utilized for cell imaging or localization, but also achieve selective imaging performed by designing probes with responsive fluorescence opening. [158]part from bioimaging, some AIEgens are endowed with PS properties which can generate cell damaging ROS upon light irradiation for photodynamic therapy or synergistic chemotherapy.In brief, the AIE@MOFs obtained by encapsulating or immobilizing AIEgens in the MOF frameworks inherit the advantages of AIEgens and the porous crystal structure of MOFs, which can show selective response imaging or increase the therapeutic effect and have received increased attention in the field of biological diagnosis and treatment. [159]s mentioned earlier, the fluorescence turn-on mode of AIEgens has more distinct recognition and higher precision.By adjusting the environment in which AIE@MOFs are located, they can respond to external stimuli, thereby enhancing fluorescence emission.Among numerous MOFs materials, zeolite imidazolate framework (ZIF) materials have been known for their simple and gentle synthesis methods, regular and adjustable pore size, large porosity and surface area, and multiresponse degradation to environment. [160]For instance, Zhang et al. simultaneously encapsulated AuNCs and quantum dots (CDs) in ZIF-8 and designed an AIE@MOFs that could degrade in response to ATP, exhibiting low cytotoxicity and enabling fluorescence imaging of ATP in living cells. [100]Zhu et al. designed a nonemission Cu-tpMOF, using TPPE as the AIEgens linker and Cu 2þ as the metal nodes and quenchers. [161]Because of the stronger binding force of GSH to Cu 2þ , Cu-tpMOF partially dissociated and emitted green fluorescence, while the acidic environment could completely dissociate and protonate it, emitting yellow fluorescence, which could be used for localization and imaging of GSH and lysosomes in cells.
In addition to preventing cancer in its early stages which poses a serious threat to human life and health, it is also crucial to ensure accurate and comprehensive treatment of tumors.Photothermal therapy (PTT) or photodynamic therapy (PDT) have become one of the promising treatment methods for tumor treatment, which is highly attractive due to its noninvasive nature, ability to reverse tumor multidrug resistance, and excellent therapeutic outcome. [119]Very different from traditional organic PSs, AIEgens could be hopeful to improve imaging and delivery performance by avoiding fluorescence quenching at tumor sites.Recently, Wang and colleagues engineered a tumor-site-activated in situ synthetic AIEgens PS for precise targeting and photodynamic therapy (Figure 7A). [162]First, two photochemically inert precursors (TPA-alkyne-2þ and MePy-N 3 ) were loaded into MOF-199 in one step and coated with F-127 to obtain PMOF NPs.After intravenous injection, two photochemically inert precursors could be catalyzed by Cu þ to generate AIEgens (TPATrzPy-3þ) by click reaction, and Cu þ derived from MOF-199 carriers degraded by GSH in tumor cells.Negatively charged AIEgens could target positively charged mitochondria and aggregate for imaging and ROS generation under light for photodynamic therapy.Precise PDT treatment and low toxicity of PMOF NPs were demonstrated in both zebrafish and mice.
Image-guided photodynamic therapy, combined with other therapies, can further improve the therapeutic effect.AIE@MOFs with active metal nodes and AIEgens ligands allow for the construction of multifunctional MOF-based AIE materials by structural design.Figure 7B shows that Wang et al. synthesized a size-transformation Fe-based AIE@MOFs therapeutic agent (Dox-PEG-PS@MIL-100 NPs). [163]The agent could respond to the weak acidity and high H 2 O 2 in the tumor microenvironment (TME) so that the MIL-100 substrates degraded and released the aggregated and luminescent PS, while the external Dox-PEG could self-assemble into nanoparticles for deep penetration to achieve the combination of PDT and chemotherapy.Dong et al. designed a program-responsive diagnostic platform based on core-shell AIE@MOFs for synergistic treatment of cancer (Figure 7C). [164]Using AIEgens and terephthalic acid as linkers and Zr 4þ as metal nodes, fluorescent A-NUiO was synthesized and hydrophobized with hydrophobic dodecanedioic acid (DCDA).Afterward, Cu-doped ZIF-8 was further encapsulated, and the weaker emitting A-NUiO@DCDA@ZIF-Cu was collected.The outer shell degraded under the low acidic pH of TME and released Cu 2þ from the frameworks which was reduced to Cu þ under the action of high GSH.Hydrophobic core A-NUiO@DCDA accumulated at the tumor site and produced fluorescent switches.Thereinto, the AIEgens could also act as PS to obtain ROS for image-guided PDT.The Cu þ obtained from the depletion of GSH could undergo Fenton-like reaction to generate •OH for chemodynamic therapy (CDT) to realize advanced photochemotherapy.Additionally, AIE@MOFs are also used in image-guided photothermal coordinated chemotherapy, exhibiting excellent ability in cancer diagnosis and synergistic therapy. [165]n summary, AIE@MOFs for biological imaging or tumor therapy can be optimally aggregated at response sites, enabling region-specific imaging or image-guided enhancement to activate phototherapy effects.Further monitoring of the efficacy of treatment to obtain an accurate prognosis may be desirable.
MOFs AIE material, so it is a promising strategy that more different metal nodes can be introduced to regulate their fluorescence properties.Last but not the least, the fluorescence emission of MOFs-based AIE materials is in the visible region (from blue to red), how to extend the emission range to the near-infrared region to increase the deep penetration ability and expand the application in biology is much required.

Other Inorganic-Based AIE Materials
In addition to the porous inorganic-based AIEgens composites mentioned above, some other inorganic materials have also been reported for assembly with AIEgens to enhance their fluorescence performance or to develop its biomedical applications, such as UCNPs and 2D thin-film materials.The later includes graphene oxide (GO), transition metal dichalcogenide (TMDs) nanosheet, layered double hydroxides (LDHs), montmorillonite (MMT), etc.

Upconversion Nanoparticles
UCNPs, as a new generation of bioluminescent markers, generally consisting of rare earth-based actinides or lanthanide-doped transition metals, are of particular interest for their applications in nanomedicine, biosensing, and in vivo bioimaging due to their excellent ability of cellular uptake, strong optical penetration while maintaining low background noise in the deep tissue level. [166,167]Guan et al. first reported an AIEgens@UCNPs nanocomposite, using UCNPs as an energy donor to generate ultraviolet or visible light by irradiation with near-infrared laser (980 nm) and photoactivate the PS AIE polymer therein by FRET effect, which effectively generates ROS in mitochondria and induces cell apoptosis. [168]This ingeniously designed structure solves both the problem of shallow penetration depth of AIEgens excited/emitted light and the problem of ACQ of conventional fluorescent materials.In addition, the emission of UCNPs can be simply tuned by changing the species and doping ratio of rare-earth ions, such as Yb 3þ , Er 3þ , and Tm 3þ , which can also meet the required excitation wavelengths of most AIEgen materials.
Regarding the latest research progress on UCNPs@AIEgens nanocomposites, Wang et al. demonstrated a nanoplatform (MUM NPs) consisting of the core MeOTTI, UCNPs@DSPE-PEG NPs (MU NPs), and MnO 2 outer shell. [169]In more detail, an amphiphilic polymer DSPE-PEG 2000 -SH was used to encapsulate hydrophobic UCNPs and AIE-active PS MeOTTI molecules by precipitation, leaving PEG 2000 -SH tails with sufficient thiol units on the outer surface.These MUM NPs enable the extension of the excitation light range from UV-vis to NIR through the FRET effect between AIE PSs and UCNPs, significantly increasing the depth of tissue penetration for Figure 8. A) Schematic diagram of nanomaterial synthesis and triple-jump photodynamic theranostics combined with fluorescence imaging-magnetic resonance imaging (FLI-MRI) dual-modality imaging.Reproduced with permission. [169]Copyright 2021, Wiley-VCH GmbH.B) Schematic diagram of the synthesis principle of UCNP-Peptide-AIEgens nanoprobe.Reproduced with permission. [170]Copyright 2021, American Chemical Society.C) Schematic illustration of fabrication of fluorescent DNA aptasensor.Reproduced with permission. [173]Copyright 2021, Wiley-VCH GmbH.D) Visualization of the fracture process of PDMS-MMT by in situ CFM.Reproduced with permission. [183]Copyright 2021, Springer Nature.
phototheranostics and •OH production (Figure 8A).In addition, TME-responsive decomposition of MnO 2 shells efficiently depleted the intracellular upregulated GSH, resulting in elevated intracellular •OH.Meanwhile, the generated Mn 2þ can implement T 1 -weighted MRI in specific tumor sites, which can be combined with AIE fluorescence imaging to achieve integrated dual-modal cancer diagnosis and treatment.Moreover, Li et al. reported an MMP3-sensitive peptide-linked AIEgens combined with UCNPs@SiO 2 , while loaded with therapeutic siRNA (Figure 8B), achieving real-time molecular imaging and inhibition of matrix metalloproteinase 3 (MMP3) accumulated in the process of Parkinson's disease (PD), thus relieving the neural stress and inflammation responses. [170]PD is associated with overexpression of (MMP3), and effective detection and inhibition of early MMP3 activity to reduce neurological stress and inflammatory response is critical for the management of PD.In this research, they demonstrated the real-time monitoring while modulating the inflammatory response of dopaminergic neurons undergoing PD development based on the constructed UCNP multifunctional nanoprobes, which showed great potential for further medicine applications due to the prevalent involvement of MMP activity in many other neurodegenerative diseases such as neuronal aging, Alzheimer's disease, etc.

Layered Inorganic Materials
Monolayer 2D materials such as GO and TMD nanosheets are generally capable of massive aggregation of fluorescent dyes due to their high specific surface area and excellent flexibility.For conventional fluorescent dye molecules, monolayer materials usually serve as efficient fluorescence quenchers.For AIE materials, they can effectively enhance the fluorescence intensity at the appropriate concentration. [171]Multilayer materials such as LDHs and MMT have received growing attention due to their greater capacity and excellent interlayer tunability compared to monolayer inorganic matrices.Multilayer inorganic substrates are generally loaded with organic fluorescent dyes using electrostatic adsorption due to their high interlayer capacity and adjustable layer spacing, thus endowing them with outstanding optical and material properties.

Graphene Oxide
Qi et al. first proposed the enrichment of 2,5-diethynylsilole (DES) NPs on the surface of GO nanosheets and successfully enhanced its fluorescence intensity and elaborated the competition between the size effect of DES NPs and the quenching effect of GO. [171] Tan et al. followed up with a systematic investigation of the fluorescence effects of monolayer TMD nanosheets, including MoS 2 , TiS 2 , and TaS 2 , on the AIE fluorophore.They demonstrated that monolayer TMD nanosheets can play dual roles in the AIE system for tuning its optical property and morphology. [172]Recently, Ma et al. demonstrated a GO-based fluorescent DNA aptasensor, [173] consisting of four ssDNA sequences that self-assemble into a DNA-tetra structure, modified with three hairpin switch aptamers to recognize target cells.Then a fluorescent probe (DSAI) and a reputable antitumor drug (DOX) were loaded in DNA-tetra skeleton respectively mainly via intercalation (Figure 8C).In this study, GO acts as a fluorescence quencher in the composite material in contrast to the fluorescence enhancement described above.Through DNA self-assembly, DNA nanomaterials containing DNA aptamer and DNA tetrahedral structure play a role of a carrier that can load both antitumor drugs and AIEgens.When reaching the target tumor cells, it detaches from the GO substrate and generates fluorescence.Similarly, Sun et al. reported a TPE-PRG material conjugated with a triple helical peptide and a TPE fluorophore, which exhibited strong fluorescence properties, using the fluorescent quencher GO substrate as a fluorescent "switch" to achieve biosensing. [174]Very recently, Zhang et al. proposed a biosensor based on AIEgens@GO for the rapid detection of SARs-CoV-2 viral sequence, a large-scale infectious disease that occurred in recent years. [175]The biosensor achieves rapid detection through two steps, the first stage is due to the automatic dissociation of the peptide receptor carried by the AIE upon encountering the target viral nucleic acid, allowing the AIEgens to detach from the GO surface thereby refluorescing, and the second stage is the formation of a nucleic acid duplex that restricts the intramolecular rotation of the AIEgens, thereby enhancing their fluorescence signal.

Transition Metal Dichalcogenides
For the TMDs-based AIEgen nanocomposites, Tebyetekerwa et al. developed a class of air-stable vertical organic-inorganic (O-I) heterostructures, represented by monolayer TMDs, such as WS 2 , WSe 2 , and MoSe 2 , which are usually located on top of the rotor of the AIE molecule with the TPE core-based structure. [176]Compared with the pristine monolayer of WS 2 , the O-I heterostructures enhance its fluorescence intensity by about 950% due to the efficient photogenerated carrier process in the AIE luminogens and the charge-transfer process in the created type I O-I heterostructures.

Layered Double Hydroxides
Li and Lu et al. first developed a hydrogen-bonding layer-by-layer (LBL) assembly method for construction of LDHs-based AIEgen ultrathin films (UTFs), [177] which efficiently enhanced the fluorescent intensity of AIEgen.Based on this study, Guan et al. fabricated two-color luminescence ultrathin films composed of LDHs and AIEgens by LBL assembly. [178]The coassembly strategy of BSPSA and PSS enables the adjustment of the fluorescent emission of UTFs, producing both green or yellow light.Recently, Ma et al. demonstrated a DES-BP4 (x%)/LDH nanocomposites and confirmed their 2D interlayer supramolecular infinite solid solutions (2D ISISSs) structure. [179]The fluorescent properties of this 2D ISISSs materials are significantly improved compared to that of pristine BP4, and the emission peak wavelength can be adjusted in the range of 490-510 nm by varying the amount of AIEgen loaded (x).This 2D ISISSs exhibit excellent fluorescence reversibility for pH and protoporphyrin, demonstrating its potential as a fluorescence biosensor for in vitro detection of pH and some biomolecules.Zhang et al. synthesized LDHs-based AIE nanocomposites with strong fluorescence, using the negatively charged AIE as a receptor for which the positively charged LDH acts as an aggregator.The efficiency of the chemiluminescence resonance energy transfer (CRET) effect can be effectively improved by controlling the donor-acceptor distance within a reasonable range or by directly enhancing the fluorescence properties of the acceptor.This study successfully amplified the weak chemiluminescence signal of ONOO-, using positively charged LDHs to capture peroxynitrite (ONOO-), providing a convenient and highly sensitive method in the field of ion detection. [180]2.4.Montmorillonite Guan et al. developed an AIE-based fluorescence imaging platform utilizing a fluorescent surfactant bound to MMT or LDH in organic-inorganic composites, which was used to visualize the macroscopic dispersion of inorganic fillers in the composites.[181] This fluorescence microscope has the advantages of tracking and visualization of inorganic fillers in composites that cannot be distinguished by conventional electron microscopy.However, the fluorescence imaging platform currently lacks a universal AIE surfactant construction strategy to be applied in different inorganic materials.Moreover, Tian et al. proposed a method of using AIEgen-active boric acid in the presence of specific covalent B-O binding to hydroxyl groups on inorganic materials such as MMT or LDH, leading to the formation of highly emissive solid-state fluorescent composites, and successfully tracked the fluorescence of inorganic fillers in organicinorganic composites.[182] This work provides a new idea for targeting inorganic materials with hydroxyl groups in polymerbased composites using a noninvasive route.By changing the affinity between inorganic materials and fluorescent molecules, it is also possible to target other inorganic materials with surfacefunctionalized amino, carboxyl, sulfhydryl, or other groups, thus completing the construction of modular systems.Recently, Peng et al. conducted a practical application study using the AIE fluorescence imaging platform.[183] They prepared a layered PDMS-MMT nanocomposite, which significantly improved its Young's modulus and toughness compared to pure PDMS and further combined AIE molecules with MMT in PDMS-MMT nanocomposite to successfully achieve 3D reconstruction of microstructure and in situ characterization of confocal fluorescence microscopy (CFM) fracture process (Figure 8D).This fluorescence microscopy characterization overcomes the obstacles of conventional electron microscopy such as interference by surface morphology, difficulty in distinguishing different components, difficulty in 3D reconstruction, etc., which provides an advanced and versatile characterization technique for organic-inorganic nanocomposites.
In summary, different various of inorganic matrix-AIE nanocomposites show their respective advantages.The ingenious structural design of UCNPs/AIEgen shifts the excitation light of AIEgens fluorescent molecules from UV-vis to NIR through FRET effect, overcoming the problem of its shallow excitation/ emission light penetration depth in biological applications, which also solves the problem of ACQ of conventional UCNP nanoprobes.Monolayer materials such as GO films can play both the roles of fluorescence enhancers and fluorescence quenchers in AIEgens nanocomposites by controlling the interlayer structure.However, there are few studies on the mechanism of interlayer structure of graphene oxide films on AIE fluorescence intensity from enhancement to quenching.Additionally, the fluorescence imaging platform constructed using the multilayer material MMT modified with AIEgens has shown great potential for application with its simplicity, high sensitivity, and ability to visualize specific inorganic fillers in organic-inorganic composites compared to conventional electron microscopy.

Conclusion Remarks and Outlook
AIE fluorescent molecules have gained widespread attention in the last decade because of their unique aggregated luminescence properties and have flourished in the fields of molecular detection, fluorescence imaging, and biomedicine.This review systematically summarized the recent advances in the inorganicbased (mainly silica and MOFs) AIE materials including their distinctive construction process, regulation of fluorescence properties, and the possible biological applications.Inspired by the restrained intramolecular rotation mechanism of AIEgens, the inorganic matrixes are able to further restrict the motion of AIEgens molecules due to their rigid structure, resulting in a highly bright and stable fluorescence signal.In addition, the inorganic matrix carrier confers better biocompatibility, outstanding stability, superior biosafety, and versatility of surface functionalization to the composite.
Although inorganic-based AIEgens nanocomposites have reaped remarkable development with their advantages, many related research results also reveal several unsolved problems or limitations in practical applications.For example, most MOF materials inherently suffer from water instability.By confining the AIEgens molecule within its framework, the fluorescence signal will no longer be stable as the material gradually disintegrates in water.In practical applications such as detection and bioimaging, there is the problem of short material luminescence lifetime.Therefore, it is necessary to carry out researches to improve the water instability of MOF materials.In addition, apart from exploiting the fluorescent properties of AIEgens, only a few studies have demonstrated the exploration of multifunctional inorganic-based AIEgens nanocomposites, such as photodynamic therapy combined with ROS generation, photoacoustic conversion, photothermal conversion, and modification of the material surface to confer targeting and therapeutic functions, which show promising prospects.Nevertheless, their long-term toxicity and dark toxicity in vivo need to be further explored.Besides, the particle size of AIE material has an important effect on its biological application.For example, in tumor treatment, the size of the particle can affect the phagocytosis and uptake of cells. [184]For the detection application, a suitable porous structure is contributed to enhance the diagnostic specificity. [185]But there is few systematic research on the relationship between the particle size of inorganic-based AIEgens materials and biological application.In the future, more suitable, multifunctional and safe materials will be discovered, which enables leapforward breakthrough in the field of biological applications of inorganic-based AIEgens materials.Moreover, fluorescence microscopy constructed using AIEgens in combination with MMT can visualize the spatial distribution of inorganic materials in organic-inorganic composites and analyze the crack motion trajectory of composites in situ, etc., which has unique advantages over conventional electron microscopy.Devices prepared by inorganic-based AIE materials will be a new fascinating direction.However, different inorganic materials require specific modifications of AIEgens molecules to bind, and there is a lack of a universal construction strategy.In the subsequent research, the binding mechanism of AIEgens molecules to inorganic materials can be explored more deeply to realize the construction of a universal organic-inorganic synthesis strategy platform.This review presents another perspective on the current research progress of inorganic-based AIEgens materials, which have a promising future with great room for improvement and are expected to have more applications in the future.

Figure 3 .
Figure 3. A) Schematic diagram of stimulus response fluorescence probe emission mechanism.Reproduced with permission.[63]Copyright 2021, Elsevier.B) AIEgens accumulate on the surface of a metal core with spacer layers.C) Studies on metal-enhanced AIEgens' fluorescence.Reproduced with permission.[64]Copyright 2022, Elsevier.D) Schematic diagram of the BTPA-PMSN chemiluminescence system.Reproduced with permission.[67]Copyright 2021, American Chemical Society.E) The luminescence principle of biological probe TR-MP and the process of monitoring pH in living cells.F) Dual-emission fluorescence spectrum of TR-MP in buffer solution with pH 3.0-9.0.Reproduced with permission.[68]Copyright 2021, Elsevier.

Figure 4 .
Figure 4. A) Workflow of the BDMSNs-MLFIA platform.Reproduced with permission.[71]Copyright 2022, Elsevier.B) HIV-I RNA-binding ligand was screened and detected by the mechanism of metal-enhanced AIEgens' fluorescence.Reproduced with permission.[74]Copyright 2022, American Chemical Society.C) Proportional fluorescent nanoprobe (N-CDs@SiO 2 @BSA-AuNCs) for the detection of glyphosate.Reproduced with permission.[75]Copyright 2023, American Chemical Society.D) Schematic diagram of synthesis process and performance evaluation of red cell membrane camouflaged silicabased AIE materials.Reproduced with permission.[77]Copyright 2022, American Chemical Society.E) Schematic diagram of the preparation process of silica-based AIE composites (Ac-700-DOX-HA) and the strategy of tumor therapy and antibacterial therapy.Reproduced with permission.[81]Copyright 2022, Wiley-VCH GmbH.
-based AIE materials can be easily synthesized through the coordination of AIEgens ligands and metal nodes or obtained by loading AIEgens through physical actions such as encapsulation of MOFs.The rigid frameworks of MOFs are suitable to restrict the intramolecular motion of AIEgens and enhance fluorescence emission.Various selection and combination of AIEgens ligands and metal nodes can simultaneously regulate the physical and chemical properties of MOFs-based AIE materials.Various functions derived from AIEgens ligands or metal nodes can give MOFs-based AIE materials multiple applications, showing great potential in detection, imaging, and biocatalytics.But more researches still need to be carried out.Most MOFsbased AIE materials are based on TPE and its derivatives, and the development and design of new AIEgens ligands is an important step to expand MOFs-based AIE materials.Additionally, there is usually only one sort of metal node in the MOFs-based