Tumor-derived covalent organic framework nanozymes for targeted chemo-photothermal combination therapy

Covalent organic frameworks (COFs) have garnered enormous attention in anti-cancer therapy recently. However, the intrinsic drawbacks such as poor biocompatibility and low target-specificity greatly restrain the full clinical implementation of COF. Herein, we report a biomimetic multifunctional COF nanozyme, which consists of AIEgen-based COF (TPE-s COF) with encapsulated gold nanoparticles ( Au NPs). The nanozyme was co-cultured with HepG2 cells until the cell membrane was fused with lipophilic TPE-s COF-Au@Cisplatin. By using the cryo-shocking method, we fabricated an inactivated form of the TPE-s COFAu@Cisplatin nanozyme endocytosed in the HepG2 cell membrane (M@TPE-s COF-Au@Cisplatin), which lost their proliferative ability and pathogenicity. Upon laser irradiation, the M@TPE-s COF-Au@Cisplatin nanozymes cleaved, thereby releasing the TPE-s COF-Au nanozyme and Cisplatin to exert their photothermal and drug therapeutic effect. This work opens a new avenue to the synthesis of tumor-derived fluorescent TPE-s COF-Au nanozymes for highly efficient, synergetic, and targeted chemo-photothermal combination therapy of liver cancer.

Automated summary

This study reports a biomimetic multifunctional COF nanozyme composed of AIEgen-based COF (TPE-s COF) and encapsulated gold nanoparticles (Au NPs). By co-culturing the nanozyme with HepG2 cells, an inactivated form of the TPE-s COF-Au@Cisplatin nanozyme (M@TPE-s COF-Au@Cisplatin) was fabricated, which lost its proliferative ability and pathogenicity. Laser irradiation resulted in the cleavage of M@TPE-s COF-Au@Cisplatin nanozymes, releasing TPE-s COF-Au nanozyme and Cisplatin for photothermal and drug therapeutic effects.