Endogenous Stimuli-Responsive Hollow Manganese Dioxide/Semiconductor Nanostructures for siRNA-Enhanced Chemotherapy

The efficacy of chemotherapeutics in cancer treatment is often limited by the complex heterogeneity of tumors and the development of drug resistance. Strategies are needed to enhance therapeutic efficacy. Herein, we present a multifunctional nanosystem based on quantum dot-modified hollow manganese dioxide (QH-MnO₂) designed for the co-delivery of paclitaxel (PTX) and survivin siRNA. This smart nanosystem leverages the tumor microenvironment (TME), specifically the elevated glutathione (GSH) levels in cancer cells, to achieve targeted and controlled drug release. Upon endocytosis, GSH-induced degradation of QH-MnO₂ triggers the release of PTX and siRNA. Simultaneously, the fluorescence of InP/ZnS quantum dots is restored, enabling real-time tracking and precise localization of the therapeutic agents. PTX disrupts microtubule dynamics, inducing mitotic arrest and apoptosis, while survivin siRNA silences the antiapoptotic survivin protein, sensitizing cancer cells to PTX and significantly enhancing therapeutic efficacy. In vivo studies demonstrated that QH-MnO₂@PTX-siRNA achieved a remarkable tumor suppression rate of 95.3% in murine models, with negligible damage to normal tissues. This innovative platform integrates tumor-responsive drug release, real-time fluorescence monitoring, and synergistic chemotherapy, offering a versatile and highly effective strategy to overcome the limitations of conventional cancer treatments.