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NK 细胞来源外泌体递送多柔比星至肝细胞癌细胞增强抗肿瘤效应:细胞毒性与凋亡研究

英文原题:Enhanced Anti-Tumor Effects of Natural Killer Cell-Derived Exosomes Through Doxorubicin Delivery to Hepatocellular Carcinoma Cells: Cytotoxicity and Apoptosis Study.

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Enhanced Anti-Tumor Effects of Natural Killer Cell-Derived Exosomes Through Doxorubicin Delivery to Hepatocellular Carcinoma Cells: Cytotoxicity and Apoptosis Study.

PubMed 2025/03/01(内容时间) Int J Mol Sci Q1 · IF 5.6(JCR 2025)

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中文摘要

外泌体是由多种细胞(包括自然杀伤(NK)细胞)分泌的纳米级细胞外囊泡,以其低毒性、高渗透性、生物相容性和强靶向能力而闻名。NK细胞来源的外泌体(NK-exos)含有增强肿瘤靶向效率的细胞毒性蛋白,使其适合用于治疗肝细胞癌(HCC)等实体瘤。尽管其在药物递送方面具有潜力,但载药NK-exos,特别是载有多柔比星(NK-exos-Dox)的NK-exos,在HCC中的作用机制仍不清楚。

本研究探讨了NK-exos-Dox对Hep3B细胞的体外抗肿瘤作用。NK-exos-Dox表达外泌体标志物(CD9和CD63)和细胞毒性蛋白(颗粒酶B和穿孔素),大小为170-220 nm。与NK-exos相比,NK-exos-Dox通过上调促凋亡蛋白(Bax、细胞色素c、cleaved caspase 3和cleaved PARP)并抑制抗凋亡蛋白(Bcl-2),增强了Hep3B细胞的细胞毒性和凋亡。这些发现表明,NK-exos-Dox通过激活特定的细胞毒性分子显著增强抗肿瘤作用,为包括HCC在内的实体瘤治疗提供了有前景的治疗机会。

展开英文摘要原文

Exosomes are nanosized extracellular vesicles secreted by various cells, including natural killer (NK) cells, and are known for their low toxicity, high permeability, biocompatibility, and strong targeting ability.

NK cell-derived exosomes (NK-exos) contain cytotoxic proteins that enhance tumor-targeting efficiency, making them suitable for treating solid tumors such as hepatocellular carcinoma (HCC). Despite their potential in drug delivery, the mechanisms of drug-loaded NK-exos, particularly those loaded with doxorubicin (NK-exos-Dox), remain unclear in HCC.

This study explored the anti-tumor effects of NK-exos-Dox against Hep3B cells in vitro . NK-exos-Dox expressed exosome markers (CD9 and CD63) and cytotoxic proteins (granzyme B and perforin) and measured 170-220 nm in size. Compared to NK-exos, NK-exos-Dox enhanced cytotoxicity and apoptosis in Hep3B cells by upregulating pro-apoptotic proteins (Bax, cytochrome c, cleaved caspase 3, and cleaved PARP) and inhibiting the anti-apoptotic protein (Bcl-2).

These findings suggest that NK-exos-Dox significantly boost anti-tumor effects by activating specific cytotoxic molecules, offering promising therapeutic opportunities for solid tumor treatment, including HCC.

论文信息

作者
Choi YH、Kim HY、Park JO、Choi E
第一作者单位
Korea Institute of Medical Microrobotics, 43-26 Cheomdangwagi-ro, Buk-gu, Gwangju 61011, Republic of Korea.South Korea
通讯作者单位
Department of Mechanical Engineering, Sogang University, 35, Baekbeom-ro, Mapo-gu, Seoul 04107, Republic of Korea.South Korea
期刊
International journal of molecular sciences2025 Mar 1
原文标识
PubMed 40076856 · DOI 10.3390/ijms26052234