Tumor-derived extracellular vesicle drug delivery system for chemo-photothermal-immune combination cancer treatment

Tumor-derived extracellular vesicle drug delivery system for chemo-photothermal-immune combination cancer treatment
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DOI:
10.1016/j.isci.2024.108833
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发表时间:
2024-02-16
期刊:
影响因子:
5.8
通讯作者:
Zhang,Ruiping
Zhang,Ruiping
中科院分区:
综合性期刊2区
文献类型:
--
作者:
Bi,Yanghui;Chen,Jieya;Zhang,Ruiping

文献摘要

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肿瘤细胞外囊泡(EV)由于其天然的长期血液循环和组织靶向能力,在药物递送和肿瘤靶向方面表现出相当大的希望。我们从小鼠乳腺癌细胞4 T1中提取EV,采用紫外线刺激和差速离心。为了创建新的纳米药物递送系统,装载有黑色素和紫杉醇白蛋白(PA)的囊泡递送系统(Vesicle delivery system,EVS),将收集的EV重复压缩在具有黑色素和PA的200 nm多孔聚碳酸酯膜上。我们的研究结果表明,乳腺癌和树突状细胞很容易吸收。当暴露于近红外光时,CD 4产生显著的光声信号和光热效应,并且可以增强小鼠肿瘤组织中CD 8 +T细胞的浸润。在体内和体外研究中,PA比PA具有更强的细胞毒性。本研究证明了当与化疗/光热/免疫疗法治疗配对时,顺铂在临床转化中的疗效。
Tumor extracellular vesicles (EVs) demonstrate considerable promise for medication delivery and tumor targeting owing to their natural long-term blood circulation and tissue targeting capabilities. We extracted EVs from mouse breast cancer cell 4T1 using UV stimulation and differential centrifugation. To create a new nano-drug delivery system, the vesicle delivery system (EPM) loaded with melanin and paclitaxel albumin (PA), the collected EVs were repeatedly compressed on a 200 nm porous polycarbonate membrane with melanin and PA. Our findings suggest that EPM is readily absorbed by breast cancer and dendritic cells. EPM generates significant photoacoustic signals and photothermal effects when exposed to near-infrared light and can enhance the infiltration of CD8+T cells in mouse tumor tissues. EPM is more cytotoxic than PA inin vivoandin vitroinvestigations. The efficacy of EPM in clinical transformation when paired with chemotherapy/photothermal/immunotherapy treatment is demonstrated in this study.