沈阳药科大学最新Cell子刊论文：铁死亡+免疫治疗，双管齐下抗肿瘤

Core Viewpoint - Ferroptosis is emerging as a promising anti-tumor therapy driven by the oxidation of polyunsaturated fatty acids in cell membranes, leading to lipid peroxidation and cell death, while also releasing damage-associated molecular patterns (DAMPs) that enhance T cell activation [1][4]. Summary by Sections Ferroptosis Mechanism and Challenges - Ferroptosis induces cell death through increased intracellular iron, reduced glutathione synthesis, and elevated reactive oxygen species (ROS) levels. However, the upregulation of PD-L1 in tumor cells can inhibit cytotoxic T cell recognition, leading to immune suppression [1][5]. Research Development - A team from Shenyang Pharmaceutical University and Shenzhen University developed a fluorinated prodrug-engineered nano-remodeler that combines a PD-L1 inhibitor (JQ1) and a ferroptosis inducer (sorafenib) to enhance oxygen supply in hypoxic tumors, significantly improving the efficacy of ferroptosis and anti-tumor immunogenicity [2][6]. Nano-remodeler Characteristics - The engineered nano-remodeler (FJSO NA) has high oxygen solubility and releases oxygen in low-pressure environments, alleviating hypoxia in solid tumors, downregulating PD-L1 expression, and enhancing ferroptosis induction and anti-tumor immune responses [6][8]. Efficacy and Safety - The study demonstrated that the nano-remodeler effectively inhibited tumor growth in various models without significant toxicity, indicating a promising direction for enhancing ferroptosis-based immunotherapy by addressing the hypoxic tumor microenvironment [8].