Abstract
Inspired by unique selectivity and irreversible destruction toward treated tissues or cells, photodynamic therapy (PDT) has gained increasing attention in cancer treatment. However, PDT-induced hypoxia and elevated glutathione (GSH) levels in cancer cells are still great challenges which can significantly reduce treatment outcomes. Herein, we designed a GSH-activatable nitric oxide (NO) generating mannan nanoparticles (NO-mannan), an “All in One” therapy nanoplatform with enhanced reactive oxygen species (ROS) generation through GSH depletion and hypoxia relief. Upon reaching the reductive hypoxic tumor microenvironment, the nanoplatform could undergo a GSH-triggered hydrophobic to hydrophilic transition and simultaneously generate NO gas with vessel-relaxing and GSH scavenging for efficient ROS production. Notably, the NO induced hypoxia relief and redox-responsive cellular antioxidant defense system destruction endowed the NO-mannan with the ability of enhanced photodynamic therapy both in vitro and in vivo. Overall, our work demonstrated a simple strategy to combine the GSH responsive NO-based gas therapy with PDT to greatly improve the PDT efficacy especially for hypoxic solid tumors, which may provide a practical paradigm for effective PDT cancer treatment.
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