Af acile approach to assemble catalase-like photosensitizing nanozymes with aself-oxygen-supplying ability was developed. The process involved Fe 3+-driven self-assembly of fluorenylmethyloxycarbonyl (Fmoc)-protected amino acids. By adding az inc(II) phthalocyanine-based photosensitizer (ZnPc) and the hypoxia-inducible factor 1(HIF-1) inhibitor acriflavine (ACF) during the Fe 3+-promoted self-assembly of Fmoc-protected cysteine (Fmoc-Cys), the nanovesicles Fmoc-Cys/Fe@Pc and Fmoc-Cys/Fe@Pc/ACF were prepared, which could be disassembled intracellularly.The released Fe 3+ could catalyze the transformation of H 2 O 2 enriched in cancer cells to oxygen efficiently,therebya meliorating the hypoxic condition and promoting the photosensitizing activity of the released ZnPc. With an additional therapeutic component, Fmoc-Cys/ Fe@Pc/ACF exhibited higher in vitro and in vivo photodynamic activities than Fmoc-Cys/Fe@Pc,d emonstrating the synergistic effect of ZnPc and ACF.

Two zinc­(II) phthalocyanines (ZnPcs) substituted with a short peptide (Gly-Gly-Lys) with either a carboxyl or a carbamoyl group at the C-terminus and an appended biotin moiety were prepared and characterized. They could self-assemble into spherical nanoparticles, namely ZnPc-GGK­(B)-COOH NP and ZnPc-GGK­(B)-CONH2 NP, through noncovalent interactions, which encapsulated the hydrophobic ZnPc units in the core and exposed the biotin moieties on the surface. The zeta potential of ZnPc-GGK­(B)-COOH NP in water was found to be −28 mV, whereas that of ZnPc-GGK­(B)-CONH2 NP was in opposite sign (+15 mV), reflecting the different functionality at the C-terminus, which also greatly affected the stability of the self-assembled nanoparticles. The targeting effect of ZnPc-GGK­(B)-COOH NP was examined against human hepatocellular carcinoma HepG2 cells, which overexpress biotin receptor, and Chinese Hamster Ovary CHO-K1 cells, which have a low expression of biotin receptor. This nanosystem was also coassembled with the chemotherapeutic doxorubicin (DOX) to form ZnPc-GGK­(B)-COOH/DOX NP. Both ZnPc-GGK­(B)-COOH NP and ZnPc-GGK­(B)-COOH/DOX NP could induce photocytotoxicity and apoptosis on HepG2 cells with an IC50 value of 1.48 and 0.49 μM ZnPc, respectively. For the latter nanosystem, the ZnPc and DOX components induced cytotoxicity in a synergistic manner. The photodynamic and chemotherapeutic effects of these two nanosystems were also examined on nude mice bearing a human colorectal adenocarcinoma HT29 tumor. The ZnPc-GGK­(B)-COOH/DOX NP exhibited a stronger tumor inhibition effect upon irradiation, demonstrating the presence of dual chemo-photodynamic therapeutic actions.

Af acile approach to assemble catalase-like photosensitizing nanozymes with aself-oxygen-supplying ability was developed. The process involved Fe 3+-driven self-assembly of fluorenylmethyloxycarbonyl (Fmoc)-protected amino acids. By adding az inc(II) phthalocyanine-based photosensitizer (ZnPc) and the hypoxia-inducible factor 1(HIF-1) inhibitor acriflavine (ACF) during the Fe 3+-promoted self-assembly of Fmoc-protected cysteine (Fmoc-Cys), the nanovesicles Fmoc-Cys/Fe@Pc and Fmoc-Cys/Fe@Pc/ACF were prepared, which could be disassembled intracellularly.The released Fe 3+ could catalyze the transformation of H 2 O 2 enriched in cancer cells to oxygen efficiently,therebya meliorating the hypoxic condition and promoting the photosensitizing activity of the released ZnPc. With an additional therapeutic component, Fmoc-Cys/ Fe@Pc/ACF exhibited higher in vitro and in vivo photodynamic activities than Fmoc-Cys/Fe@Pc,d emonstrating the synergistic effect of ZnPc and ACF.