Ren Caixia, Zhang Haoyuan, Yang Min, Huang Yanjun, Guo Juan, Chen Kexin, Fu Yaning, Chen Huan, Cao Yuanyuan, Hao Rongzhang, Hou Hongwei
Department of Toxicology and Sanitary Chemistry, School of Public Health, Capital Medical University, Beijing 100069, China.
Beijing Key Laboratory of Environment and Aging, Beijing 100069, China.
ACS Appl Mater Interfaces. 2025 Jun 25;17(25):37053-37067. doi: 10.1021/acsami.5c05076. Epub 2025 Jun 11.
Cancer remains a leading global cause of death, with conventional therapies often limited. While immune therapy has revolutionized cancer therapy with the use of immune agents, its efficacy is often curtailed by the immunosuppressive tumor microenvironment (TME). To address the limited effectiveness of existing immunotherapies, we developed a multifunctional biomimetic nanocomposite, tumor cell membrane-coated hollow manganese nitrogen carbon nanocomposite (HMn-NC@M), integrating phototherapy and immunotherapy. HMn-NC@M enhances tumor targeting and performs photothermal and photodynamic therapy under near-infrared light, inducing immunogenic cell death (ICD), releasing tumor antigens and damage-associated molecular patterns (DAMPs). This triggers antitumor immune responses while modulating the tumor microenvironment by decomposing hydrogen peroxide, alleviating hypoxia, depleting glutathione, and releasing Mn ions. Mn activates the cGAS-STING pathway, amplifying ICD-induced immunity, promoting dendritic cell maturation, and enhancing cytotoxic infiltration. Transcriptome profiling of models unveiled the activation of key pathways governing tumor proliferation, apoptosis, and immune modulation. Evaluation of models demonstrated tumor suppression of 44% with monotherapy and 92% with the combination of phototherapy and immunotherapy, highlighting the potential of HMn-NC@M as a multifunctional nanotherapeutic platform for cancer therapy.
癌症仍然是全球主要的死亡原因,传统疗法往往存在局限性。虽然免疫疗法通过使用免疫制剂彻底改变了癌症治疗方式,但其疗效常常受到免疫抑制性肿瘤微环境(TME)的限制。为了解决现有免疫疗法有效性有限的问题,我们开发了一种多功能仿生纳米复合材料,即肿瘤细胞膜包覆的中空锰氮碳纳米复合材料(HMn-NC@M),它整合了光疗和免疫疗法。HMn-NC@M增强了肿瘤靶向性,并在近红外光下进行光热和光动力疗法,诱导免疫原性细胞死亡(ICD),释放肿瘤抗原和损伤相关分子模式(DAMPs)。这触发了抗肿瘤免疫反应,同时通过分解过氧化氢、缓解缺氧、消耗谷胱甘肽和释放锰离子来调节肿瘤微环境。锰激活cGAS-STING通路,放大ICD诱导的免疫反应,促进树突状细胞成熟,并增强细胞毒性浸润。对模型的转录组分析揭示了控制肿瘤增殖、凋亡和免疫调节的关键通路的激活。对模型的评估表明,单一疗法的肿瘤抑制率为44%,光疗和免疫疗法联合使用时为92%,突出了HMn-NC@M作为一种多功能纳米治疗平台用于癌症治疗的潜力。