A CaCO₃-based nanoplatform with sonodynamic and tumor microenvironment activated for combined in vitro cancer therapy

Introduction: Sonodynamic therapy (SDT) has potential clinical applications for cancer therapy, and is yet restricted by complex tumor microenvironmental (TME) factors. Thus, the research problem of TME modulation as well as efficient tumor treatment still needs to be clarified. Method: In this study, a calcium carbonate (CaCO₃) nanoplatform was designed for ultrasound (US) and TME response-triggered, which encapsulated Ag₂S and loaded with L-Arg, and further wrapped with RBC/Platelet membrane, named as QD@Ca/M_L-Arg. Results: Non-invasive US-triggered SDT by Ag₂S and acidic environment-responsive drug release were achieved. In vitro experiments validated the efficacy of SDT, Ca-ion interference and nitric oxide (NO) gas therapy as combined therapy for cancer treatment. By means of RNA sequencing, the cancer therapeutic mechanism of SDT in redox-related pathways was elucidated. The immunosuppressive TME was simulated with a M2-macrophage/cancer cell co-culture system to confirm the immune activating effect of immunogenic cell death (ICD). Conclusion: Accordingly, the potential of QD@Ca/M_L-Arg-was demonstrated for in vitro TME modulation, cancer therapeutic efficacy and clinical translation.