Modulating Pore Wall Chemistry Empowers Sonodynamic Activity of Two-Dimensional Covalent Organic Framework Heterojunctions for Pro-Oxidative Nanotherapy.

Covalent organic frameworks (COFs) have garnered growing interest in the field of biomedicine; however, their application in sonodynamic therapy remains underexplored due to limited understanding of their intrinsic activity and structure-property relationships. Here, we present a pore wall chemistry modulation strategy for empowering sonodynamic activity to two-dimensional (2D) COF heterojunctions through in situ growth of COFs on bismuth oxycarbonate nanosheets (B NSs). Compared to the negligible sonodynamic effects observed in the pristine B NSs, the 2D heterojunction with vinyl-decorated COF pore walls demonstrates a 3.6-fold enhancement in sonocatalytic singlet oxygen generation. This performance also significantly outperforms that of isoreticular COFs functionalized with methoxy or non-substituted groups. Mechanistic studies reveal that the vinyl groups in the B@COF (BC) heterojunction facilitate the separation and transfer of charge carriers while also enhancing the adsorption of oxygen molecules. Furthermore, peroxymonosulfate (PMS) loading into the porous COFs boosts the therapeutic efficacy of antitumor nanotherapy via sonocatalytic dual oxidative species generation. These findings underscore the critical role of pore wall chemistry in modulating the sonocatalytic properties of COFs, and advance the development of COF-based sonosensitizers for pro-oxidative applications.