Metal-Organic Frameworks@Au Nanoreactor as an Oxidative Stress Amplifier for Enhanced Tumor Photodynamic Therapy through the Alleviation of Hypoxemia and the Depletion of Glutathione

Recently, photodynamic therapy (PDT) based on the generation of cytotoxic reactive oxygen species (ROS) has drawn great attention in tumor treatment. However, the hypoxia tumor micro environment (TME) inhibits the generation efficacy of ROS, and the high glutathione (GSH) level in TME could neutralize the generated ROS, both of which strongly reduce the therapeutic efficiency of PDT. In this work, we first constructed the porphyrinic metal-organic framework PCN-224. Then Au nanoparticles were decorated on the PCN-224 to obtain the PCN-224@Au. The decorated Au nanoparticles could not only produce O2 through the decomposition of H2O2 in tumor sites for enhancing the generation of 1O2 in PDT but also deplete glutathione through the strong interactions between Au and sulfhydryl groups on glutathione to weaken the antioxidant ability of tumor cells, thus amplifying the 1O2 damage to cancer cells. The in vitro and in vivo experiments totally exhibited that the as-prepared PCN224@Au nanoreactor can be used as an oxidative stress amplifier for enhanced PDT, which provides a promising candidate to conquer the limitation of intratumor hypoxia and high GSH level on PDT of cancer.

Automated summary

Photodynamic therapy (PDT) based on the generation of reactive oxygen species (ROS) has gained attention in tumor treatment. However, the hypoxic tumor microenvironment inhibits ROS generation and high glutathione levels neutralize ROS, reducing the effectiveness of PDT. This study constructs porphyrinic metal-organic framework PCN-224 and decorates it with gold nanoparticles (PCN-224@Au) to enhance ROS generation and deplete glutathione, amplifying damage to cancer cells. In vitro and in vivo experiments demonstrate that PCN-224@Au can serve as an oxidative stress amplifier for enhanced PDT, providing a promising solution for addressing intratumor hypoxia and high GSH levels.