Biodegradable Mesoporous Organosilica Nanosheets for Chemotherapy/Mild Thermotherapy of Cancer: Fast Internalization, High Cellular Uptake, and High Drug Loading

The choice of nanocarriers is crucial to fabricate ideal therapeutic nanoplatform in the treatment of cancer. Considering the advantages brought by the two-dimensional (2D) materials with atomic thickness in drug loading and cellular uptake, herein, novel 2D biodegradable mesoporous organosilica nanosheets (MONSs) are presented, and their application in chemotherapy/mild thermotherapy of cancer is studied by loading chemotherapy drug doxorubicin (DOX) and conjugating ultrasmall CuS nanoparticles. It is found that the loading of DOX in MONSs is as high as 859 μg/mg due to their large surface area and intermediate void structure. The release of DOX from MONSs is intelligently controlled by pH value, glutathione (GSH) concentration, and laser irradiation. Excitingly, in comparison with traditional spherical mesoporous organosilica nanoparticles, as-prepared MONSs not only show more rapid degradation but also exhibit faster internalization and higher cellular uptake efficiency due to their larger aspect ratios and unique cellular internalization approach of 2D materials. A mild thermotherapy induced by ultrasmall CuS nanoparticles can further promote the cellular uptake and improve chemotherapy efficacy. The in vitro and in vivo experimental results reveal that the theranostic nanoplatform based on degradable MONSs has excellent biocompatibility and anticancer effects. Therefore, MONSs are expected to be a competitive alternative to existing silica-based nanomaterials in antitumor treatment.