Chen Liang, Huang Jierou, Liu Li, Tong Ming, He Xinchun, Zhao Shaojing, Diao Qingxu, Chen Haiou, Zeng Jie, Lan Minhuan, Yi Jianing
Department of Infectious Diseases, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, China.
Department of Rheumatology and Immunology, Hunan Provincial People's Hospital, The First Affiliated Hospital of Hunan Normal University, Changsha, 410005, Hunan, China.
Biomaterials. 2026 Feb;325:123634. doi: 10.1016/j.biomaterials.2025.123634. Epub 2025 Aug 11.
Effective immuno-photodynamic therapy (IPDT) is impeded by the limitations of monotherapy approaches, inadequate immune activation, and an immunosuppressive tumor microenvironment (TME). Here, we present a multifunctional phototheranostic nanoplatform based on an A-D-A type photovoltaic molecule (ITCC), which self-assembles into water-soluble nanoparticles (ITCC NPs) via DSPE-PEG-NH-2000. Upon near-infrared (NIR) irradiation, ITCC NPs generate reactive oxygen species (ROS) and heat, enabling synergistic photodynamic therapy (PDT) and photothermal therapy (PTT), thereby sequentially triggering immunogenic cell death (ICD), activating the cGAS-STING pathway, and promoting vascular normalization. These cascade effects collectively promote dendritic cells (DCs), natural killer (NK) and T cell activation and infiltration, suppress regulatory T (Treg) cells, and reprogram both systemic and tumor immune microenvironments. Co-administration of the immune checkpoint inhibitor anti-TIGIT (aTIGIT), targeting phototherapy-induced exhausted TIGIT NK cells, further potentiates antitumor efficacy. Metabolomic analysis reveals ITCC NP-induced reprogramming of tyrosine and lipid metabolism, potentially relieving immunosuppressive metabolic stress and enhancing antitumor immunity. In summary, ITCC NPs function as a single-component, NIR-activated nanoplatform that elicits synergistic phototherapeutic and immunomodulatory effects for cascade amplification of antitumor immunity. Their therapeutic potential is also validated in human hepatocellular carcinoma and breast cancer organoid models.
有效的免疫光动力疗法（IPDT）受到单一疗法方法的局限性、免疫激活不足和免疫抑制肿瘤微环境（TME）的阻碍。在此，我们展示了一种基于A-D-A型光伏分子（ITCC）的多功能光诊疗纳米平台，该分子通过DSPE-PEG-NH-2000自组装成水溶性纳米颗粒（ITCC NPs）。在近红外（NIR）照射下，ITCC NPs产生活性氧（ROS）和热量，实现协同光动力疗法（PDT）和光热疗法（PTT），从而依次触发免疫原性细胞死亡（ICD），激活cGAS-STING途径，并促进血管正常化。这些级联效应共同促进树突状细胞（DCs）、自然杀伤（NK）细胞和T细胞的激活与浸润，抑制调节性T（Treg）细胞，并重新编程全身和肿瘤免疫微环境。联合使用靶向光疗诱导的耗竭性TIGIT NK细胞的免疫检查点抑制剂抗TIGIT（aTIGIT），进一步增强抗肿瘤疗效。代谢组学分析揭示了ITCC NPs诱导的酪氨酸和脂质代谢重编程，可能缓解免疫抑制性代谢应激并增强抗肿瘤免疫力。总之，ITCC NPs作为一种单组分、近红外激活的纳米平台，引发协同光疗和免疫调节作用，用于抗肿瘤免疫的级联放大。它们的治疗潜力也在人肝细胞癌和乳腺癌类器官模型中得到验证。
