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

Chunyu Huang,Wei Liu,Chunping Liu,Liang Du,Shuntao Wang,Zeming Liu,Mingzhu Chen,Yongfa Zheng

doi:10.1186/s12951-021-01182-y

Abstract

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 ·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.Graphical

Highlights

Despite advances in scientific study, cancer, which can strike at any age, remains a severe threat to human life and health in today’s society [1,2,3]
RT relies on the use of high-energy X-rays or gamma rays to cause radiation-induced DNA damage or to stimulate the formation of large amounts of toxic reactive oxygen species (ROS), of which about 90% are produced by mitochondria [7]
Nanozymes have great advantages over natural enzymes [18,19,20]. FeS2 nanozyme can reduce GSH and catalyze H2O2 to produce sufficient ·OH to destroy mitochondria, which is expected to achieve a good synergistic effect combined with radiotherapy [21]

Summary

Introduction

Despite advances in scientific study, cancer, which can strike at any age, remains a severe threat to human life and health in today’s society [1,2,3]. *Correspondence: zyftgwz1986@163.com; wliu@whu.edu.cn †Chunyu Huang and Zeming Liu contributed to this work 1 Key Laboratory of Artificial Micro‐ and Nano‐Structures of Ministry of Education, School of Physics and Technology, Wuhan University, Wuhan 430072, People’s Republic of China 2 Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China Full list of author information is available at the end of the article Reducing GSH level can effectively improve RT efficacy.

Results

Conclusion