Li Cheng-Lei, Zhang Wen-Zhong, Zhao Rui-Rui, Le Jing-Qing, Zhang Bing-Chen, Xie Huan-Zhang, Lu Yu-Sheng, Shao Jing-Wei
Fujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and Chemotherapy, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China.
Department of Laboratory Medicine, DongguanInstitute of Clinical Cancer Research, The Tenth Affiliated Hospital of Southern Medical University (Dongguan people's hospital), Dongguan, Guangdong 523058, China.
Colloids Surf B Biointerfaces. 2025 Nov;255:114908. doi: 10.1016/j.colsurfb.2025.114908. Epub 2025 Jun 27.
Immune checkpoint blockade (ICB) holds broad application prospects in tumor treatment. However, the poor immunogenicity and the adaptive resistance cells severely limit the clinical efficacy. Immunogenic cell death (ICD) can sensitize the cells which were initially lower responsive to ICB. Based on this, we reported a metal coordination co-assembly nanocomposite (SIF NPs), which can enhance cancer immunotherapy by strengthening ICD induction through inducing ferroptosis-photo-chemo. The SIF NPs possess excellent biocompatibility and stability, and exhibit good PTT and PDT effects both in vitro and in vivo. The SIF NPs disrupt redox homeostasis and induce ferroptosis by consuming glutathione (GSH), downregulating the expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4), and enhancing the generation of lipid hydroperoxides (LPO). Importantly, SIF NPs trigger an ICD cascade via inducing the cell death, thus enhancing the immunogenicity of tumors. In a tumor-bearing mice model, the synergistic therapy of SIF NPs and anti-PD-L1 antibody demonstrated a powerful inhibition effectiveness on bilateral tumors and instigated a long-time immune memory effect. This study indicates that the combined treatment of ferroptosis-photo-chemo and immunotherapy possess promising application prospects.
免疫检查点阻断（ICB）在肿瘤治疗中具有广阔的应用前景。然而，免疫原性差和适应性抗性细胞严重限制了临床疗效。免疫原性细胞死亡（ICD）可使最初对ICB反应较低的细胞敏感化。基于此，我们报道了一种金属配位共组装纳米复合材料（SIF NPs），它可以通过诱导铁死亡-光化学疗法增强ICD诱导，从而增强癌症免疫治疗。SIF NPs具有优异的生物相容性和稳定性，在体外和体内均表现出良好的光热治疗（PTT）和光动力治疗（PDT）效果。SIF NPs通过消耗谷胱甘肽（GSH）、下调溶质载体家族7成员11（SLC7A11）和谷胱甘肽过氧化物酶4（GPX4）的表达以及增强脂质氢过氧化物（LPO）的生成来破坏氧化还原稳态并诱导铁死亡。重要的是，SIF NPs通过诱导细胞死亡触发ICD级联反应，从而增强肿瘤的免疫原性。在荷瘤小鼠模型中，SIF NPs与抗PD-L1抗体的联合治疗对双侧肿瘤表现出强大的抑制效果，并激发了长期的免疫记忆效应。这项研究表明，铁死亡-光化学疗法与免疫疗法的联合治疗具有广阔的应用前景。
