Xu Yu, Liao Jianping, Wang Jiahong, Gao Yuan, Wu Yuan, Gao Meiqin, Liu Wenwen, Zhang Da, Zhang Wenmin, Huang Aimin
Department of Pathology, School of Basic Medical Sciences, Fujian Medical University, 88 Jiaotong Road, Fuzhou, 350004, Fujian, China.
Institute of Oncology, Fujian Medical University, 88 Jiaotong Road, Fuzhou, 350004, Fujian, China.
J Transl Med. 2025 Jun 13;23(1):653. doi: 10.1186/s12967-025-06636-7.
Vascular abnormalities and hypoxia in solid tumors limit the efficacy of chimeric antigen receptor (CAR) T-cell therapy. This study proposes a biomimic nanoenzyme, Lenv@BSA-PtNPs, combining platinum nanoparticles (PtNPs) and lenvatinib, to address these challenges in a hepatocellular carcinoma (HCC) nonobese diabetic (NOD) mice model.
Lenv@BSA-PtNPs were designed using albumin as a solubilizer, embedding lenvatinib via hydrophobic interactions and facilitating in situ PtNPs generation. The nanoenzyme functions as a catalase, converting HO to O, downregulating hypoxia-inducible factor (HIF-1), and normalizing tumor vasculature. Its efficacy was evaluated in a glypican-3 (GPC3)-CAR T-cell therapy model for HCC.
Lenv@BSA-PtNPs significantly improved tumor oxygenation, normalized vasculature, and enhanced GPC3-CAR T-cell infiltration into tumors. This led to potent antitumor effects and prolonged survival in the HCC mouse model.
Lenv@BSA-PtNPs provide a simple and effective strategy to enhance CAR-T cell accumulation and efficacy by ameliorating hypoxia and normalizing tumor vasculature, offering a promising approach for improving CAR-T therapy in solid tumors.
实体瘤中的血管异常和缺氧限制了嵌合抗原受体（CAR）T细胞疗法的疗效。本研究提出了一种将铂纳米颗粒（PtNPs）与乐伐替尼相结合的仿生纳米酶Lenv@BSA-PtNPs，以解决肝细胞癌（HCC）非肥胖糖尿病（NOD）小鼠模型中的这些挑战。
以白蛋白作为增溶剂设计Lenv@BSA-PtNPs，通过疏水相互作用包埋乐伐替尼并促进原位生成PtNPs。该纳米酶发挥过氧化氢酶的作用，将H₂O₂转化为O₂，下调缺氧诱导因子（HIF-1）并使肿瘤血管正常化。在用于HCC的磷脂酰肌醇蛋白聚糖-3（GPC3）-CAR T细胞治疗模型中评估其疗效。
Lenv@BSA-PtNPs显著改善了肿瘤氧合，使血管正常化，并增强了GPC3-CAR T细胞向肿瘤内的浸润。这导致了HCC小鼠模型中强大的抗肿瘤作用并延长了生存期。
Lenv@BSA-PtNPs通过改善缺氧和使肿瘤血管正常化，提供了一种简单有效的策略来增强CAR-T细胞的聚集和疗效，为改善实体瘤中的CAR-T治疗提供了一种有前景的方法。
