The combination of
chemotherapy and
photodynamic therapy provides a promising approach for enhanced
tumor eradication by overcoming the limitations of each individual therapeutic modality. However,
tumor is pathologically featured with extreme
hypoxia together with the adaptable overexpression of
anti-oxidants, such as
glutathione (GSH), which greatly restricts the therapeutic efficiency. Here, a combinatorial strategy was designed to simultaneously relieve tumor hypoxia by self-oxygenation and reduce intracellular GSH level to sensitize chemo-
photodynamic therapy. In our system, a novel multi-functional nanosystem based on MnO2-doped
graphene oxide (GO) was developed to co-load
cisplatin (CisPt) and a
photosensitizer (Ce6). With MnO2 doping, the nanosystem was equipped with intelligent functionalities: (1) catalyzes the decomposition of H2O2 into
oxygen to relieve the tumor hypoxia; (2) depletes GSH level in
tumor cells, and (3) concomitantly generates Mn2+ to proceed Fenton-like reaction, all of which contribute to the enhanced anti-
tumor efficacy. Meanwhile, the surface
hyaluronic acid (HA) modification could facilitate the targeted delivery of the nanosystem into
tumor cells, thereby resulting in amplified cellular toxicity, as well as
tumor growth inhibition in nude mice model. This work sheds a new light on the development of intelligent nanosystems for synergistic combination
therapy via regulating tumor microenvironment.