A phthalocyanine‑derived covalent organic framework nanoplatform with boosted sonodynamic efficacy for apigenin co‑delivery and combined antitumor therapy.

Sonodynamic therapy (SDT), characterized by its non-invasiveness and high tissue penetration depth, has emerged as a promising novel antitumor treatment modality. Nevertheless, the development of efficient sonosensitizers for SDT still poses a challenge. In this study, a covalent organic framework based on zinc phthalocyanines (ZnPc-COF) was synthesized. It was discovered that ZnPc-COF exhibited significantly enhanced sonodynamic activity compared to free ZnPc. This study focuses on the adverse impacts of highly expressed HIF-1α at tumor sites on tumor treatment. Therefore, by leveraging the porous structure of ZnPc-COF, we adsorbed HIF-1α inhibitor apigenin (API) and modified the surface of ZnPc-COF with polyethylene glycol (PEG) and the targeting peptide TAT (trans-activator of transcription) to obtain the final product ZnPc-COF/API@DSPE-TAT. The research indicates that ZnPc-COF/API@DSPE-TAT possesses excellent sonodynamic activity and demonstrates a combined cytotoxic effect of SDT and API. In in vivo experiments, it was confirmed that ZnPc-COF/API@DSPE-TAT has remarkable tumor-targeting ability, significantly reduces HIF-1α level in tumors, and can effectively inhibit tumor growth. The construction mechanism and combined antitumor strategy of ZnPc-COF/API@DSPE-TAT offer theoretical and practical guidance for the development of new sonosensitizers.