Tumor-derived biomimetic nanozyme with immune evasion ability for synergistically enhanced low dose radiotherapy

High doses of radiation can cause serious side effects and efficient radiosensitizers are urgently needed. To overcome this problem, we developed a biomimetic nanozyme system (CF) by coating pyrite (FeS2) into tumor-derived exosomes for enhanced low-dose radiotherapy (RT). CF system give FeS2 with immune escape and homologous targeting abilities. After administration, CF with both glutathione oxidase (GSH-OXD) and peroxidase (POD) activities can significantly lower the content of GSH in tumor tissues and catalyze intracellular hydrogen peroxide (H2O2) to produce a large amount of center dot OH for intracellular redox homeostasis disruption and mitochondria destruction, thus reducing RT resistance. Experiments in vivo and in vitro showed that combining CF with RT (2 Gy) can provide a substantial suppression of tumor proliferation. This is the first attempt to use exosomes bionic FeS2 nanozyme for realizing low-dose RT, which broaden the prospects of nanozymes.

Automated summary

The research developed an effective radiosensitizer - biomimetic nanozyme system CF, which coats pyrite FeS2 in tumor-derived exosomes to enhance low-dose radiotherapy. The CF system has immune escape and homologous targeting abilities, reducing GSH content in tumor tissues and disrupting intracellular redox homeostasis to inhibit tumor proliferation.