Covalent Organic Framework Nanocages with Enhanced Carrier Utilization and Cavitation Effect for Cancer Sonodynamic...

Ultrasound (US)-triggered sonodynamic therapy (SDT) is an emerging method for treating cancer due to its non-invasive nature and high-depth tissue penetration ability. However, current sonosensitizers commonly have unsatisfactory quantum yields of free radicals. In this work, we have developed unique organic semiconductor π-conjugated covalent organic framework nanocages (COFNs) as highly efficient sonosensitizers to boost free radical (¹O₂ and ^•OH) production and cancer therapy. With the hollow and porous structure and band transport behavior, COFNs displayed remarkably improved SDT performance through enhanced electron utilization and cavitation effect, with a 1.8-fold increase in US pressure and a 64.8% increase in ¹O₂ production relative to the core-shell-structured COF under US irradiation. The in vitro and in vivo experimental results verified the elevated SDT performance, showing a high tumor suppression of 91.4% against refractory breast cancer in mice. This work provides a promising strategy to develop high-performance sonosensitizers for cancer therapy.