Efficient catalysis of endogenous oxygen generation for MRI-guided synergistic photodynamic therapy by ternary nanostructure

Abstract

Tumor hypoxic microenvironment is a crucial bottleneck limiting its clinical therapeutic efficacy. Therefore, how to design nano-drugs with clear structure and function based on the characteristics of the tumor microenvironment to overcome the hypoxia of tumors and achieve high-efficiency and low-toxicity treatment is an important strategy to solve the problem of tumor treatment. Herein, we design and synthesize a ternary nano-platform, Ce6-AuCeFe, with longan structure by a simple method to obtain Magnetic Resonance Imaging (MRI)-guided cascade reagent to enhance cancer Photodynamic therapy (PDT). The AuCeFe was synthesized via a one-pot reaction with controlled morphology and loaded with Ce6 to assist PDT. Ce6-AuCeFe was synthesized as a hybrid nanocatalyst model of glucose oxidase and peroxidase mimics because of its outstanding catalytic performance. As nontoxic glucose was continuously converted to abundant H2O2 by AuCeFe, the excess H2O2 was subsequently catalyzed by the peroxidase-like activity of AuCeFe to generate O2, which helped to alleviate the hypoxic tumor microenvironment. The mechanistic studies elucidate that the ternary nanoparticles facilitate triplet oxygen into singlet oxygen through energy transfer, which leads to highly toxic reactive oxygen species (ROS) production combined with PDT, achieving much desirable cancer cells killing effect under hypoxia conditions. Meanwhile, the degradation of Ce6-AuCeFe under tumor microenvironment also enhanced on T1 and T2-weighted MRI, indicating that Ce6-AuCeFe could be used as two-mode MRI contrast agents for precisely guiding in therapy. In summary, our study provides a novel strategy for tumor therapy by utilizing well-structured metal composites to achieve high-efficiency oxygen production, thereby overcoming the hypoxic tumor microenvironment.