Nanoscale coordination polymers enabling antioxidants inhibition for enhanced chemodynamic therapy

Reactive oxygen species (ROS) generation to induce cell death is an effective strategy for cancer therapy. In particular, chemodynamic therapy (CDT), using Fenton-type reactions to generate highly cytotoxic hydroxyl radical (center dot OH), is a promising treatment modality. However, the therapeutic efficacy of ROS-based cancer treatment is still limited by some critical challenges, such as overexpression of enzymatic and non-enzymatic antioxidants by tumor cells, as well as the low tumor targeting efficiency of therapeutic agents. To address those problems, biomimetic Cu-Zn protoporphyrin IX nanoscale coordination polymers have been developed, which significantly amplify oxidative stress against tumors by simultaneously inhibiting enzymatic and nonenzymatic antioxidants and initiating the CDT. In this design, cancer cell membrane camouflaged nanoparticle exhibits an excellent homotypic targeting effect. After being endocytosed into tumor cells, the nanoparticles induce depletion of the main non-enzymatic antioxidant glutathione (GSH) by undergoing a redox reaction with GSH. Afterward, the redox reaction generated cuprous ion (Cu+) works as a CDT agent for center dot OH generation. Furthermore, the released Zn protoporphyrin IX strongly inhibits the activity of the typical enzymatic antioxidant heme oxygenase-1. This tetra-modal synergistic strategy endows the biomimetic nanoparticles with great capability for anticancer therapy, which has been demonstrated in both in vitro and in vivo studies.

Automated summary

Reactive oxygen species (ROS) generation for cell death induction is effective in cancer therapy. However, the limited therapeutic efficacy of ROS-based cancer treatment is due to challenges such as overexpression of antioxidants by tumor cells and low targeting efficiency of therapeutic agents. To address these issues, biomimetic Cu-Zn protoporphyrin IX nanoscale coordination polymers have been developed to inhibit antioxidants and initiate chemodynamic therapy (CDT). These nanoparticles show excellent homotypic targeting effect and can induce depletion of non-enzymatic antioxidants and generate cytotoxic hydroxyl radicals (center dot OH) for cancer treatment.