Target Functionalized Carbon Dot Nanozymes with Dual‐Model Photoacoustic and Fluorescence Imaging for Visual Therapy in Atherosclerosis

Abstract Multifunctional nanomedicines have been used in atherosclerosis theranostics. Herein, phosphatidylserine‐specific peptide CLIKKPF‐functionalized carbon‐dots nanozymes (pep‐CDs) are reported for specific and efficient noninvasive theranostic of atherosclerosis. Surprisingly, pep‐CDs are discovered to not only inherit the inherent properties of carbon dots (CDs), including deep‐red fluorescence emission, photoacoustic response, and superoxide dismutase‐like antioxidant, and anti‐inflammatory activities but also possess the ability to target recognition on foam cells and target localization on plaques due to the specific interaction of CLIKKPF with phosphatidylserine on the membrane outer surface of foam cells. Furthermore, the target localization effect of pep‐CDs vastly promotes the efficient accumulation of CDs in plaque, thus maximizing AS theranostic of CDs. Interestingly, pep‐CDs could be developed to image plaque for monitoring atherosclerosis pathological progression in real‐time resulting from the different content of foam cells. This work on the one hand proposes a simple and feasible strategy to construct theranostic nanoplatform employing only a single functional unit (i.e., multifunctional CDs) to simplify the fabrication procedure, on the other hand, highlights the advantages of the active target auxiliary mode for atherosclerosis theranostic applications.


Figure S1 .
Figure S1.Hydrodynamic diameter of CDs and pep-CDs.

Figure S2 .
Figure S2.A) XPS survey spectra and high resolution B) N 1s, C) C 1s, D) O 1s, and E) S 2p spectra of CDs.

Figure S3 .
Figure S3.FT-IR spectra of CDs and pep-CDs.

Figure S4 .Figure
Figure S4.A) UV-Vis absorption spectra of CDs at different concentrations.B) Calibration curve of the absorption intensity of CDs at 675 nm versus the corresponding concentration.C) UV-Vis absorption spectra of pep-CDs at different concentrations.

Figure S6 .
Figure S6.FL excitation spectra of CDs and pep-CDs.

Figure S7 .
Figure S7.A) Digital photographs of 10 μg/mL pep-CDs in different media during the whole observation period from 0 to 6 d (from left to right are H2O, PBS and DMEM.).B-D) FL emission spectra (λex = 420 nm) and stability of 10 μg/mL

Figure S8 .
Figure S8.UV-Vis absorption spectra of DPPH • after incubation with different concentrations of CDs, and the corresponding absorbance of each system and the elimination efficiency of DPPH • by CDs.Data were illustrated as mean ± s.d.(n = 3).

Figure S9 .
Figure S9.UV-Vis absorption spectra of ABTS •+ after incubation with different concentrations of CDs, and the corresponding absorbance of each system and the elimination efficiency of ABTS •+ by CDs.Data were illustrated as mean ± s.d.(n = 3).

Figure S10 .
Figure S10.UV-Vis absorption spectra of • OH after incubation with different concentrations of CDs, and the corresponding absorbance of each system and the elimination efficiency of • OH by CDs.Data were illustrated as mean ± s.d.(n = 3).

Figure S11 .
Figure S11.UV-Vis absorption spectra of O2 •-after incubation with different concentrations of CDs, and the corresponding absorbance of each system and the elimination efficiency of O2 •-by CDs.Data were illustrated as mean ± s.d.(n = 3).

Figure S13 .
Figure S13.A) CLSM images and B) corresponding quantitative analysis of FL signal intensities of RAW264.7 macrophages pre-incubated with ox-LDL for 48 h and

Figure S15 .
Figure S15.Digital photos and hemolysis rates of mice blood processed with water (positive control (+)), PBS (negative control (-)), and pep-CDs at various

Figure S16 .
Figure S16.Ex vivo FL images and corresponding quantitative analysis of FL signal intensities of health and AS aortas from C57 and ApoE −/− mice fed on HFD for 10 w at 2 h post CDs i.v.injection.Data were illustrated as mean ± s.d.(n = 3).*p < 0.05,.

Figure S17 .
Figure S17.In vivo pharmacokinetic performance of pep-CDs after i.v.injection in mice.Data were illustrated as mean ± s.d.(n = 3).

Figure S18 .
Figure S18.FL images and corresponding quantitative analysis of FL signal intensities of the major organs (heart, liver, spleen, lung, and kidney) from ApoE −/− mice fed on HFD for 10 w at various time points after i.v.injection of pep-CDs.Data were illustrated as mean ± s.d.(n = 3).*p < 0.05.

Table S2 .
Detection result of the free peptides in pep-CDs.