Radiation therapy, a fundamental treatment for tumors, is often accompanied by radiation-induced skin injury (RISI). Excessive production of reactive oxygen species (ROS) and subsequent inflammation are two key factors in RISI development that will cause skin injury and affect radiotherapy. Herein, the co-assembled binary polyphenol natural products inspired the development of a dual-functional cascade microneedle system for prevention and treatment of RISI. Specifically, epigallocatechin gallate (EGCG) and curcumin (CUR) were co-assembled into nanoparticles (CEPG) by intermolecular interactions and then incorporated with catalase (CAT) to achieve a cascade system in the microneedles (this microneedle system was conducive to penetrate into the epidermal keratinocytes where RISI had the greatest impact). When using microneedles, the tip dissolved rapidly and delivered CEPG and CAT into the dermis, where CEPG NPs were able to respond to ROS and decompose into EGCG and CUR. More importantly, EGCG and CAT formed a cascade that converts superoxide anions into water step-by-step, which can reduce cell damage caused by free radicals in the early stages of radiation for prevention; meanwhile, CUR inhibited inflammatory pathways, achieving the treatment of skin inflammation in the post-radiotherapy period. These explorations broaden the strategy for the application of natural products in RISI.
Keywords: coassembly; curcumin; epigallocatechin gallate; microneedle; radiation-induced skin injury.