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近红外二区光驱动纳米马达增强光免疫治疗肝细胞癌。

NIR-II Light-Actuated Nanomotors for Enhanced Photoimmunotherapy Toward Hepatocellular Carcinoma.

机构信息

NMPA Key Laboratory for Research and Evaluation of Drug Metabolism & Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.

Department of Ultrasound, Harbin Medical University Cancer Hospital, Harbin 150081, China.

出版信息

ACS Appl Mater Interfaces. 2024 Jul 31;16(30):39051-39063. doi: 10.1021/acsami.4c06994. Epub 2024 Jul 19.

Abstract

Light-propelled nanomotors, which can convert external light into mechanical motion, have shown considerable potential in the construction of a new generation of drug delivery systems. However, the therapeutic efficacy of light-driven nanomotors is always unsatisfactory due to the limited penetration depth of near-infrared-I (NIR-I) light and the inherent biocompatibility of the motor itself. Herein, an asymmetric nanomotor (Pd@ZIF-8/R848@M JNMs) with efficient motion capability is successfully constructed for enhanced photoimmunotherapy toward hepatocellular carcinoma. Under near-infrared-II (NIR-II) irradiation, Pd@ZIF-8/R848@M JNMs convert light energy into heat energy, exhibiting self-thermophoretic locomotion to penetrate deeper into tumor tissues to achieve photothermal therapy. At the same time, functionalized with an immune-activated agent Resiquimod (R848), our nanomotors could convert a "cold tumor" into a "hot tumor", transforming the immunosuppressive microenvironment into an immune-activated state, thus achieving immunotherapy. Dual photoimmunotherapy of the as-developed NIR-II light-driven Pd@ZIF-8/R848@M JNMs demonstrates considerable tumor inhibition effects, offering a promising therapeutic approach in the field of anticancer therapy.

摘要

光驱动纳米马达能够将外部光转化为机械运动,在构建新一代药物输送系统方面显示出了相当大的潜力。然而,由于近红外-I(NIR-I)光的有限穿透深度和马达本身固有的生物相容性,光驱动纳米马达的治疗效果总是不尽人意。在此,我们成功构建了一种具有高效运动能力的不对称纳米马达(Pd@ZIF-8/R848@M JNMs),用于增强对肝细胞癌的光免疫治疗。在近红外-II(NIR-II)照射下,Pd@ZIF-8/R848@M JNMs 将光能转化为热能,表现出自热泳动,能够穿透更深的肿瘤组织,实现光热治疗。同时,通过功能化免疫激活剂 Resiquimod(R848),我们的纳米马达可以将“冷肿瘤”转化为“热肿瘤”,将免疫抑制微环境转化为免疫激活状态,从而实现免疫治疗。所开发的 NIR-II 光驱动 Pd@ZIF-8/R848@M JNMs 的双重光免疫治疗显示出了相当大的肿瘤抑制效果,为癌症治疗领域提供了一种有前途的治疗方法。

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