Intestinal delivery of ROS-scavenging carbonized polymer dots for full-course treatment of acute and chronic radiation enteritis

Abstract

Radiation enteritis is an unavoidable complication of radiotherapy for pelvic tumors that seriously affects the prognosis of cancer patients. The fundamental mechanism inducing cell death and tissue injury is the generation of excessive reactive oxygen species (ROS) by ionizing radiation. In the present study, we developed novel S-doped red fluorescent carbonized polymer dots (S-rCPDs) with high biocompatibility and efficient ROS-scavenging capability to act as an intestinal protective agent against radiation damage. The S-rCPDs significantly eliminates cellular ROS and alleviates DNA damage under X-ray radiation. To achieve drug accumulation within the distal intestine, S-rCPDs loaded pH-controlled release polymer microspheres (S-rCPDs@MPs) is produced via microfluidic technology. In vivo experimental results show that oral administration of S-rCPDs@MPs effectively suppresses the secretion of pro-inflammatory cytokines and alleviates acute radiation intestinal injury, with a better protective effect than amifostine, which is hereto the only clinically approved radioprotector. Moreover, the as-prepared S-rCPDs@MPs could stabilize the balance of intestinal flora and continuously downregulate the expression of transforming growth factor β1 (TGF-β1), eventually inhibiting the progression of chronic intestinal fibrosis. This study provides a novel strategy for whole-course treatment of radiation enteritis using CPDs-based materials, which could inspire the development of other radioprotective nano-drugs.