Supplementary file 1_Ultrasound-controllable carbon monoxide nano-delivery systems for combined sonodynamic/gaseous therapies.docx

IndroductionThe integration of sonodynamic therapy (SDT) and carbon monoxide (CO) presents a promising synergistic strategy in cancer therapy owing to the unique advantage of CO in SDT sensitization. However, the development of SDT-compatible CO-delivery nanosystems remain a substantial challenge.
MethodsHere, we developed an ultrastable and controllable CO nanoreservoir system through the integration of chlorine e6 (Ce6)-loaded, cancer cell membrane coating and iron carbonyl (Fe3CO12)-bridged mesoporous silica bodies (Fe3CO12-MSNs), which was specifically engineered to simultaneously achieve SDT and ultrasound (US)-responsive sustained CO release. Owing to the stabilization of Fe3CO12 within the silica framework, Fe3CO12-MSNs not only decreased unwanted CO leakage during transport but also enabled US-responsive matrix degradation accompanied by sustained CO release at tumor sites, which prolongs the therapeutic window of CO and maximizes the synergy of SDT and CO therapy.
Results and DiscussionThis nanoplatform-mediated combination therapies showed highly efficient antitumor effects and triggered a robust tumor-specific immune responses. When in combination with immune checkpoint blockers, the nanoplatform notably eradicate the breast cancer with low systematic toxicity. Overall, our work provides a promising nanoplatform with US-responsive and sustainable CO release for highly efficient and safe SDT/CO combined therapeis.