A tumor pH-responsive autocatalytic nanoreactor as a H2O2 and O2 self-supplying depot for enhanced ROS-based chemo/photodynamic therapy. (December 2022) - Liu, Furong
Abstract: Combining the internal force-driven chemodynamic therapy (CDT) and the external energy-triggered photodynamic therapy (PDT) holds great promise to achieve an advanced anticancer effect based on reactive oxygen species (ROS). However, the insufficient oxy-substrates supply in tumor microenvironment, like hydrogen peroxide (H2 O2 ) and oxygen (O2 ), is the Achilles heel that greatly restricts the efficacy of this ROS-based treatment. Herein, the construction of a c opper pe roxide-based tumor pH-res ponsive a utocatalytic nanor eactor (CESAR), via an albumin-mediated biomimetic mineralization strategy is described. The decoration of human serum albumin endows the nanoreactor good hydrophilicity and biocompatibility, which is highly desired for the metal-based materials. Upon exposure to acidic tumor microenvironment, CESAR presents a pH-triggered disintegration with Cu 2+, H2 O2 and O2 generated instantly. The generated H2 O2 complements the hyperoxide deficiency and initiates a localized Fenton-like reaction with the assistance of Cu 2+ for highly toxic hydroxyl radicals (OH) production for improving CDT. The evolved O2 gas enables hypoxia relief for enhanced Ce6-mediated PDT. This H2 O2 /O2 self-supplying strategy significantly amplifies the tumor oxidative damage and gains an optimal treatment outcome, which offers a new paradigm for optimizing the tumor therapeutic options limited by oxide or hyperoxide deficiency, not only for CDT/PDT, but also other oxy-substrates involved strategies. Statement of significance: The shortage of oxy-substrates in the tumor microenvironment remains a great challenge for ROS-based cancer therapy. Herein, we introduce human serum albumin as a scaffold to stabilize copper peroxide nanomaterials for constant production of H2 O2 and O2 to enhance chemodynamic/photodynamic therapy. The tumor pH-triggered H2 O2 /O2 production and Cu 2+ release are confirmed, assuring the strategy of a highly precise, effective way to destroy tumor without any side effects. This work lends new and exciting insights into the engineering design of autocatalytic oxy-substrates self-supply nanoreactor for overcoming the bottlenecks, like the oxy-substrates deficiency of CDT/PDT and the poor stability of metal peroxides, to achieve highly effective chemodynamic/photodynamic therapy. Graphical abstract: Image, graphical abstract