Platelet Membrane Biomimetic Manganese Carbonate Nanoparticles Promote Breast Cancer Stem Cell Clearance for Sensitized Radiotherapy

Introduction: The presence of cancer stem cells (CSCs) significantly limits the therapeutic efficacy of radiotherapy (RT). Efficient elimination of potential CSCs is crucial for enhancing the effectiveness of RT. Methods: In this study, we developed a biomimetic hybrid nano-system (PMC) composed of MnCO 3 as the inner core and platelet membrane (PM) as the outer shell. By exploiting the specific recognition properties of membrane surface proteins, PMC enables precise targeting of CSCs. Sonodynamic therapy (SDT) was employed using manganese carbonate nanoparticles (MnCO 3 NPs), which generate abundant reactive oxygen species (ROS) upon ultrasound (US) irradiation, thereby impairing CSC self-renewal capacity and eradicating CSCs. Subsequent RT effectively eliminates common tumor cells. Results: Both in vitro cell experiments and in vivo animal studies demonstrate that SDT mediated by PMC synergistically enhances RT to selectively combat CSCs while inhibiting tumor growth without noticeable side effects. Discussion: Our findings offer novel insights for enhancing the efficacy and safety profiles of RT. Keywords: cancer stem cells clearance, radiosensitization, platelet membrane, sonodynamic therapy, manganese carbonate nanoparticles