Oxygen-Independent Photocleavage of Radical Nanogenerator for Near-IR-Gated and H2O-Mediated Free-Radical Nanotherapy

The oxygen-dependent nature and limited penetration capacity of visible light render the low efficiency of photodynamic therapy in hypoxic and deep-seated tumors. Therefore, the development of oxygen-free photoactivated chemotherapy (PACT) to generate cytotoxic reactive oxygen species by near-IR (NIR) light-cleavable photocages is in high demand. Here, an oxygen-irrelevant PACT strategy based on NIR light-triggered hydroxyl radicals (center dot OH) generation is developed for free-radical nanotherapy. Blebbistatin-loaded upconversion of mesoporous silica nanoparticles (UCSNs-B) is established to facilitate the high loading efficiency of blebbistatin and implement the efficient transformation of NIR light into blue light for unprecedented direct photorelease of oxygen-independent center dot OH. Under NIR laser irradiation, UCSNs-B converted NIR light into blue light, thus enabling the photocleavage of blebbistatin to induce the burst of center dot OH. The center dot OH burst under NIR laser irradiation further induces cancer cell apoptosis and significant suppression of hypoxic tumors. In addition, the gadolinium ion (Gd3+)-doped UCSNs-B are used as contrast agents in magnetic resonance imaging to facilitate real-time monitoring of the therapeutic processes. This study effectively demonstrates that the UCSNs-B act as NIR light-triggered photocages to facilitate oxygen-irrelevant center dot OH bursts, thus providing insights into the development of efficient PACT nanoagents for cancer treatment.

Automated summary

This study develops an oxygen-irrelevant PACT strategy based on NIR light-triggered hydroxyl radicals (center dot OH) generation for free-radical nanotherapy.