Self-Assembled EGCG Nanoparticles with Enhanced Intracellular ROS Scavenging for Skin Radioprotection

Xiaowen Han,1 Ruiling Xu,1 Yang Xia,2 Ying Liu,3 Shan Chen,3 Mingsong Shi,1 Zhiyan Zou,1 Yuanyuan Liang,1 Tingting Chen,1 Yufeng Tang,4 Wei Tang,3 Xiaoan Li,1,5 Liangxue Zhou2,6,7 1NHC Key Laboratory of Nuclear Technology Medical Transformation, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 2Department of Neurosurgery, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 3Institute of Materials, China Academy of Engineering Physics, Jiangyou, 621907, People’s Republic of China; 4Department of Neurology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 5Department of Gastroenterology, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China; 6Department of Neurosurgery, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, 610041, People’s Republic of China; 7Department of Neurosurgery, the Fifth People’s Hospital of Ningxia, Shizuishan, Ningxia, 753000, People’s Republic of ChinaCorrespondence: Xiaoan Li; Liangxue Zhou, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Mianyang, 621000, People’s Republic of China, Email [email protected]; [email protected]: Skin radiation damage is a prevalent form of tissue injury encountered during radiotherapy, radiation accidents, and occupational exposure. The only clinically approved radioprotective agent, amifostine, is associated with numerous side effects, underscoring the urgent need for the development of safe and effective radioprotective agents. Natural products with reductive properties possess high antioxidant activity and biocompatibility, but their low bioavailability limits their radioprotective efficacy and clinical application. To address this, we utilized epigallocatechin gallate (EGCG) as a model compound and employed nanotechnology to enhance cellular uptake of natural compounds, thereby improving their free radical scavenging capabilities.Methods: EGCG nanoparticles (EGCG NPs) with robust intracellular reactive oxygen species (ROS) scavenging ability were prepared via self-assembly. The morphology, size distribution, and antioxidant capacity of EGCG NPs were characterized. Cytocompatibility, intracellular ROS levels and DNA damage, cell migration and immune response of EGCG NPs to macrophages were tested in vitro. The in vivo radiation protection and biocompatibility of EGCG NPs were assessed in murine model.Results: The EGCG NPs was successfully prepared and compared to free EGCG, EGCG NPs demonstrated better cellular uptake, significantly enhancing their biocompatibility, intracellular ROS scavenging capacity, and ability to mitigate DNA damage. Furthermore, EGCG NPs facilitated fibroblast proliferation and migration, while inhibiting the polarization of macrophages towards the M1 phenotype in vitro. In animal levels, EGCG NPs exhibited markedly improved radioprotective efficacy over free EGCG, effectively reducing skin edema and ulceration, alleviating pathological conditions such as interstitial edema, dermal fluid accumulation, and inflammatory infiltration, decreasing the duration of skin injury, and promoting wound healing.Conclusion: This work offers novel insights into the therapeutic application of EGCG NPs as a potential alternative for skin radioprotection and provides a powerful approach for developing radioprotective agents derived from natural products. Keywords: radiation-induced skin injury, nanoparticles, free radicals scavenging, radioprotection