Xu Jianxiang, Zhang Yanyan, Zheng Yilu, Wang Tong, Zhang Huan, Wang Kai, Wang Yu, Williams Gareth R, Zhu Li-Min
College of Biological Science and Medical Engineering, Shanghai Engineering Research Center of Nano-Biomaterials and Regenerative Medicine, Donghua University, Shanghai 201620, PR China.
International Union Laboratory on Acupuncture Based Target Discovery, International Joint Laboratory on Acupuncture Neuro-immunology, Shanghai Research Institute of Acupuncture and Meridian, Yue Yang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200030, China.
Carbohydr Polym. 2025 Mar 1;351:123120. doi: 10.1016/j.carbpol.2024.123120. Epub 2024 Dec 5.
In this work we present a near-infrared (NIR)-operated nanoswitch based on chitosan nanoparticles (EpCAM-CS-co-PNVCL@IR780/IMQ NPs) that induces cascade immunogenic tumor ferroptosis via cytokine storm. The formulation was prepared by loading a photosensitiser (IR780) and an immunotherapeutic drug (imiquimod; IMQ) into temperature- and pH-responsive chitosan-based NPs functionalized with tumor-targeting aptamers. The EpCAM aptamer can chaperone the NPs selectively into cancer cells, and allow them to enter the cell nucleus. In vitro and in vivo assays revelaed that the NPs were able to effectively induce the immunogenic ferroptosis of cancer cells. Under NIR irradiation, EpCAM-CS-co-PNVCL@IR780/IMQ cause cell death in tumors via photothermal therapy. Moreover, IMQ promotes the maturation of dendritic cells (DCs), which then activate cytotoxic T-lymphocytes (CTLs); these T-cells go on to provide immunotherapy of metastatic tumor cells. The metastatic tumor cells can be induced to undergo ferroptosis by the addition of arachidonic acid (AA), which interacts with interferon cytokines (IFN-γ) released from CTLs.
在这项工作中，我们展示了一种基于壳聚糖纳米颗粒（EpCAM-CS-co-PNVCL@IR780/IMQ NPs）的近红外（NIR）操作纳米开关，该纳米开关通过细胞因子风暴诱导级联免疫原性肿瘤铁死亡。该制剂是通过将光敏剂（IR780）和免疫治疗药物（咪喹莫特；IMQ）负载到用肿瘤靶向适体功能化的温度和pH响应性壳聚糖基纳米颗粒中制备的。EpCAM适体可以将纳米颗粒选择性地带入癌细胞，并使其进入细胞核。体外和体内试验表明，这些纳米颗粒能够有效诱导癌细胞的免疫原性铁死亡。在近红外照射下，EpCAM-CS-co-PNVCL@IR780/IMQ通过光热疗法导致肿瘤细胞死亡。此外，IMQ促进树突状细胞（DCs）成熟，进而激活细胞毒性T淋巴细胞（CTLs）;这些T细胞继续为转移性肿瘤细胞提供免疫治疗。通过添加花生四烯酸（AA）可以诱导转移性肿瘤细胞发生铁死亡，花生四烯酸与CTLs释放的干扰素细胞因子（IFN-γ）相互作用。
