In Situ One‐Pot Synthesis of MOF–Polydopamine Hybrid Nanogels with Enhanced Photothermal Effect for Targeted Cancer Therapy

Abstract Herein, a simple one‐pot way is designed to prepare a type of multifunctional metal–organic framework (MOF)‐based hybrid nanogels by in situ hybridization of dopamine monomer in the skeleton of MnCo. The resultant hybrid nanoparticles (named as MCP) show enhanced photothermal conversion efficiency in comparison with pure polydopamine or MnCo nanoparticles (NPs) synthesized under a similar method and, therefore, show great potential for photothermal therapy (PTT) in vivo. The MCP NPs are expected to possess T 1 positive magnetic resonance imaging ability due to the high‐spin Mn‐N6 (S = 5/2) in the skeleton of MnCo. To improve the therapy efficiency as a PTT agent, the MCP NPs are further modified with functional polyethylene glycol (PEG) and thiol terminal cyclic arginine–glycine–aspartic acid peptide, respectively: the first one is to increase the stability, biocompatibility, and blood circulation time of MCP NPs in vivo; the second one is to increase the tumor accumulation of MCP‐PEG NPs and improve their therapeutic efficiency as photothermal agent.

In Vitro Cellular Toxicity Test: HeLa human cervical cancer cells and 4T1 murine breast cancer cells were originally obtained from American Type Culture Collection (ATCC).
Human cervical carcinoma (HeLa) cells were cultured in 96-well plates at 1×10 4 cells per well and incubated in 5% CO 2 at 37 ºC for 24 h. Then different concentrations of MnCo and MCP-PEG (12.5, 25, 50, 100, and 200 g mL -1 ) were added. After that, the cells were further incubated for 24 h, and excess unbound materials were washed for three times with PBS.
Subsequently, the relative cell viabilities (%) were detected by the standard MTT assay.
For in vitro photothermal therapy, HeLa and 4T1 cancer cells were seeded into 96-well plates and then incubated with various concentrations of MCP−PEG at 37 °C. Then the cells were exposed to an 808 nm NIR laser at the power density of 1.0 W cm -2 for 5 min. The relative cell viabilities after photothermal ablation were measured using the standard MTT assay. For imaging, HeLa cancer cells incubated with MCP-PEG (50 µg mL -1 ) after irradiation by the 808 nm laser at various power density of 0, 0.2, 0.4, 0.8, 1.2, 1.6 W cm -2 for 5 min were stained by calcein AM and PI and then imaged using a microscope. The apoptosis and necrosis induced by photothermal toxicity were evaluated by flow cytometry. HeLa cells (1×10 4 ) were seeded into a 12-well plate and incubated with MCP-PEG (50 µg mL -1       Assuming that the weight of PDA is x g and MnCo is y g (MCP is x+y=100 g).

Calculation of photothermal conversion efficiency:
The photothermal conversion efficiency of MCP-PEG and PDA-PEG were calculated using the model described in Roper's et al. 2 where the photothermal conversion efficiency is described by the following equations: where m and C p are the mass and heat capacity of solvent (water), respectively. T is the solution temperature. Q NPs is the photothermal energy input by nanoparticle. Q diss is the heat associated with the light absorbance of the solvent. Q loss is thermal energy lost to the surroundings. 12 where represents the photothermal conversion efficiency. A 808 is the absorbance intensity of nanoparticle at 808 nm. I is the power density of laser (1.0 W/cm 2 ).
When the temperature of system reaching a steady stage, dT/dt in equation (1) is 0. Then, Q NPs + Q diss = Q loss = hST max , and we get equation (4).
To calculate hS: We herein introduce θ =T/T max , which is defined as the ratio of ΔT to ΔT max . Then equation (1) will be change to equation (5).
When the laser was shut off (the cooling stage), the Q NPs +Q diss = 0, equation (5) will be changed to equation (6).