Zou Qingshuang, Liao Ke, Li Guangchao, Huang Xin, Zheng Yongwei, Yang Gun, Luo Min, Xue Evelyn Y, Lan Chuanqing, Wang Shuai, Shen Yao, Luo Dixian, Ng Dennis K P, Liu Quan
Department of Laboratory Medicine, Huazhong University of Science and Technology Union Shenzhen Hospital (Nanshan Hospital), Shenzhen University, Shenzhen, 518052, China.
Department of Chemistry, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong, 999077, China.
Adv Mater. 2025 Jan;37(2):e2407425. doi: 10.1002/adma.202407425. Epub 2024 Jul 1.
The infiltration and cytotoxicity of chimeric antigen receptor (CAR)-T cells are crucial for effective elimination of solid tumors. While metallo-immunotherapy is a promising strategy that can activate the antitumor immunity, its role in promoting CAR-T cell therapy remains elusive. The first single-element nanomaterial based on chromium nanoparticles (Cr NPs) for cancer photo-metallo-immunotherapy has been reported previously. Herein, an extended study using biodegradable polydopamine as a versatile carrier for these nanoparticles, enabling synergistic CAR-T cell therapy, is reported. The results show that these nanocomposites with or without further encapsulation of the anticancer drug alpelisib can promote the CAR-T cell migration and antitumor effect. Upon irradiation with near-infrared light, they caused mild hyperthermia that can "warm" the "cold" tumor microenvironment (TME). The administration of B7-H3 CAR-T cells to NOD severe combined immunodeficiency gamma mice bearing a human hepatoma or PIK3CA-mutated breast tumor can significantly inhibit the tumor growth after the induction of tumor hyperthermia by the nanocomposites and promote the secretion of serum cytokines, including IL-2, IFN-γ, and TNF-α. The trivalent Cr ions, which are the major degradation product of these nanocomposites, can increase the CXCL13 and CCL3 chemokine expressions to generate tertiary lymphoid structures (TLSs) in the tumor tissues, facilitating the CAR-T cell infiltration.
嵌合抗原受体（CAR）-T细胞的浸润和细胞毒性对于有效消除实体瘤至关重要。虽然金属免疫疗法是一种有前景的可激活抗肿瘤免疫的策略，但其在促进CAR-T细胞治疗中的作用仍不清楚。先前已报道了第一种基于铬纳米颗粒（Cr NPs）的用于癌症光金属免疫疗法的单元素纳米材料。在此，报道了一项扩展研究，使用可生物降解的聚多巴胺作为这些纳米颗粒的通用载体，实现协同CAR-T细胞治疗。结果表明，这些有或没有进一步包裹抗癌药物阿培利司的纳米复合材料可以促进CAR-T细胞迁移和抗肿瘤作用。在用近红外光照射后，它们会引起轻度热疗，可“温暖”“冷”肿瘤微环境（TME）。将B7-H3 CAR-T细胞给予携带人肝癌或PIK3CA突变乳腺癌的NOD重度联合免疫缺陷γ小鼠，在纳米复合材料诱导肿瘤热疗后可显著抑制肿瘤生长，并促进血清细胞因子的分泌，包括白细胞介素-2、干扰素-γ和肿瘤坏死因子-α。这些纳米复合材料的主要降解产物三价铬离子可增加CXCL13和CCL3趋化因子的表达，在肿瘤组织中生成三级淋巴结构（TLSs），促进CAR-T细胞浸润。
