Constructing Activatable Photosensitizers Using Covalently Modified Mesoporous Silica

The combination of photosensitizers (PSs) and nanomaterials is a widely used strategy to enhance PS efficacy and broaden their applicability. However, the current nanocarrier-based delivery strategies focus on conventional PSs, neglecting the critical issue of PS phototoxicity. In this study, DHUOCl-25, an activatable PS (aPS) activated by hypochlorous acid, is synthesized by combining a silicon source structure and an activation unit. DHUOCl-25 functions as a silica source for synthesizing activatable mesoporous silica nanostrctures (MSNs) using a standardized protocol, enabling the synthesis of aPS-covalently modified MSNs for a variety of biologic therapeutic applications. On one hand, the resulting nano-aPS maintains aPS functionality for antibacterial application by achieving synergistic antibacterial action via MB PDT and retained cetyltrimethylammonium bromide (CTAB) (antibacterial agent) (DHU-MSNs-2). On the other hand, the nano-aPS exhibits MSN properties for drug loading, facilitating the synergistic integration of photodynamic therapy with chemotherapy (DHU-MSNs-6) of tumors and demonstrating efficacy against the spinal metastases of lung cancer. These results validate this strategy for developing novel aPSs and expanding the application of aPSs and MSNs.