Dual Regulation of Energy/Electron Transfer in MOF@COP Heterojunctions through Ingenious Molecular Engineering for Enhanced Sonodynamic Cancer Therapy

Sonosensitization-mediated reactive oxygen species generation associated with energy and electron transfer is an essential process of sonodynamic therapy. However, the development of sonosensitizers with both high intersystem crossing (ISC) rates and efficient carrier separation remains greatly challenging. Herein, we present a new scheme to construct a class of heterojunctions (MC-R, R = −H, −OCH 3, −Br) by Zr-based metal–organic framework (NU-901) and porphyrin-based covalent organic polymers (COPs) with different substituents. In this sonocatalytic system, the type-II heterojunction based on NU-901 and COPs can effectively promote the separation of electron–hole pairs, increasing the generation of superoxide anions, while the introduction of substituents (−OCH 3, −Br) can extend the conjugation of COPs by p-π binding and enhance spin–orbit coupling through heavy atom effects, which could regulate the ISC process and improve the quantum yield of singlet oxygen. Remarkably, MC-Br as a representative MC-R exhibits the best tumor inhibition efficiency in vivo.