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基于黑磷的纳米颗粒诱导肝癌细胞线粒体凋亡和免疫细胞肿瘤浸润以增强树突状细胞治疗

英文原题:Black phosphorus-based nanoparticles induce liver cancer cell mitochondrial apoptosis and immune cell tumor infiltration for enhancing dendritic cell therapy.

查看英文原题

Black phosphorus-based nanoparticles induce liver cancer cell mitochondrial apoptosis and immune cell tumor infiltration for enhancing dendritic cell therapy.

PubMed 2024/03/02(内容时间) Heliyon

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中文摘要

细胞免疫治疗是当前肿瘤免疫治疗的重要组成部分,但其面临免疫细胞功能障碍、新抗原识别有限以及淋巴细胞向肿瘤微环境浸润不足等挑战。

本研究提出了一种新方法,利用基于树突状细胞(DC)的细胞免疫治疗与光热纳米佐剂黑磷(BP)纳米颗粒的联合应用来克服这些挑战。一种名为PLGA@BP-R848的新平台,由将聚乳酸-羟基乙酸共聚物(PLGA)修饰到负载免疫佐剂R848的BP纳米片上组成。PLGA@BP-R848纳米颗粒表现出优异的药物递送和释放能力,以及光热效应、生物相容性,并能激活线粒体凋亡通路Blc-2-Bax-细胞色素c-caspase-3并抑制PI3K-AKT-mTOR信号通路。在肝细胞癌小鼠模型中,PLGA@BP-R848纳米颗粒与GPC3肽致敏的树突状细胞结合,成功诱导了全身性抗肿瘤免疫反应。PLGA@BP-R848纳米颗粒增强了免疫细胞向肿瘤的浸润并诱导癌细胞凋亡。树突状细胞与光热纳米佐剂的协同治疗有效抑制了肿瘤生长,并促进了肿瘤中三级淋巴结构(TLS)的形成。

本研究提出了一种利用光热纳米佐剂提升细胞免疫治疗(如DCs治疗)抗肿瘤效果的新方法。

展开英文摘要原文

Cellular immunotherapy is a crucial aspect of current tumor immunotherapy, though it presents several challenges such as immune cell dysfunction, limited recognition of neoantigens, and inadequate lymphocyte infiltration into the tumor microenvironment.

This study proposes a novel approach utilizing a combination of dendritic cell (DC)-based cellular immunotherapy and a photothermal nanoadjuvant black phosphorus (BP) nanoparticles to overcome these challenges. A new platform called PLGA@BP-R848, which consists of modifying poly-(lactic- co -glycolic acid) (PLGA) onto BP nanosheets loading the immune adjuvant R848. The PLGA@BP-R848 nanoparticles demonstrated exceptional drug delivery and release capabilities, as well as a photothermal effect, biocompatibility, and the ability to activate the mitochondrial apoptotic pathway Blc-2-Bax-Cytochrome c-caspase-3 and inhibit the PI3K-AKT-mTOR signaling pathway.

In a hepatocellular carcinoma mouse model, the binding of PLGA@BP-R848 nanoparticles and dendritic cells primed with GPC3 peptides, successfully induced a systemic anti-tumor immune response. PLGA@BP-R848 nanoparticles bolster immune cell infiltration into tumors and induce cancer cell apoptosis. The synergistic therapy involving dendritic cells and photothermal nanoadjuvant effectively suppressed tumor growth, and facilitated the formation of tertiary lymphatic structures (TLS) in tumors.

This study presents a novel approach in using photothermal nanoadjuvants to advance antitumor effect of cellular immunotherapy, such as DCs therapy.

论文信息

作者
Liao K、Chen S、Yang G、Huang X、Wang T、Long S、Wang J、Yin L
单位
Institute of Pharmacy and Pharmacology, School of Pharmaceutical Science, Hengyang Medical School, University of South China, Hengyang, Hunan, 421001, PR China.China
期刊
Heliyon2024 Mar 15
原文标识
PubMed 38463812 · DOI 10.1016/j.heliyon.2024.e27234