Octadecyl Gallate and Lipid-modified MnSe 2 Nanoparticles Enhance Radiosensitivity in Esophageal Squamous Cell Carcinoma and Promote Radioprotection in Normal Tissues.

Radiotherapy, a widely used therapeutic strategy for esophageal squamous cell carcinoma (ESCC), is always limited by radioresistance of tumor tissues and side-effects on normal tissues. Herein, a signature based on 4 core genes of cGAS-STING pathway, is developed to predict prognosis and assess immune cell infiltration, indicating that the cGAS-STING pathway and radiotherapy efficacy are closely intertwined in ESCC. A novel lipid-modified manganese diselenide nanoparticle (MnSe 2 -lipid) with extraordinarily uniform sphere morphology and tumor microenvironment (TME) responsiveness is developed to simultaneously overcome radioresistance and reduce side-effects of radiation. The uniform MnSe 2 encapsulated lipid effectively achieves tumor accumulation. Octadecyl gallate (OGA) on surface of MnSe 2 forming pH-responsive metal-phenolic covalent realizes rapid degradation in TME. The released Mn 2+ promotes radiosensitivity by generating reactive oxygen species (ROS) induced by Fenton-like reaction and activating cGAS-STING pathway. Spontaneously, selenium strengthens immune response by promoting secretion of cytokines and increasing white blood cells (WBC), and performs antioxidant activity to reduce side-effects of radiotherapy. Overall, this multifunctional remedy which is responsive to TME is capable of providing radiosensitivity by cGAS-STING pathway-mediated immunostimulation and chemodynamic therapy (CDT), and radioprotection of normal tissues, is highlighted here to optimize ESCC treatment. This article is protected by copyright. All rights reserved.