Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy.,Nature Communications

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Tumor exosome-based nanoparticles are efficient drug carriers for chemotherapy.
Nature Communications ( IF 14.7 ) Pub Date : 2019-08-23 , DOI: 10.1038/s41467-019-11718-4
Tuying Yong _{1,

2} , Xiaoqiong Zhang ₁ , Nana Bie ₁ , Hongbo Zhang ₃ , Xuting Zhang ₁ , Fuying Li ₁ , Abdul Hakeem ₁ , Jun Hu ₁ , Lu Gan _{1,

2} , Hélder A Santos _{4,

5} , Xiangliang Yang _{1,

2}

Affiliation

Developing biomimetic nanoparticles without loss of the integrity of proteins remains a major challenge in cancer chemotherapy. Here, we develop a biocompatible tumor-cell-exocytosed exosome-biomimetic porous silicon nanoparticles (PSiNPs) as drug carrier for targeted cancer chemotherapy. Exosome-sheathed doxorubicin-loaded PSiNPs (DOX@E-PSiNPs), generated by exocytosis of the endocytosed DOX-loaded PSiNPs from tumor cells, exhibit enhanced tumor accumulation, extravasation from blood vessels and penetration into deep tumor parenchyma following intravenous administration. In addition, DOX@E-PSiNPs, regardless of their origin, possess significant cellular uptake and cytotoxicity in both bulk cancer cells and cancer stem cells (CSCs). These properties endow DOX@E-PSiNPs with great in vivo enrichment in total tumor cells and side population cells with features of CSCs, resulting in anticancer activity and CSCs reduction in subcutaneous, orthotopic and metastatic tumor models. These results provide a proof-of-concept for the use of exosome-biomimetic nanoparticles exocytosed from tumor cells as a promising drug carrier for efficient cancer chemotherapy.

中文翻译：

基于肿瘤外泌体的纳米颗粒是用于化疗的有效药物载体。

在不损失蛋白质完整性的情况下开发仿生纳米颗粒仍然是癌症化学疗法中的主要挑战。在这里，我们开发了一种生物相容性的肿瘤细胞分泌的外泌体仿生多孔硅纳米颗粒（PSiNPs）作为靶向癌症化疗的药物载体。外来鞘的阿霉素负载的PSiNPs（DOX @ E-PSiNPs）是由肿瘤细胞内吞DOX的PSiNPs胞吐作用产生的，在静脉内给药后表现出增强的肿瘤积累，血管渗出和渗透到深部的肿瘤实质。此外，DOX @ E-PSiNPs不论其来源如何，在散装癌细胞和癌干细胞（CSC）中均具有显着的细胞摄取和细胞毒性。这些特性使DOX @ E-PSiNPs在具有CSCs特征的总肿瘤细胞和侧群细胞中具有极大的体内富集，从而在皮下，原位和转移性肿瘤模型中产生了抗癌活性并降低了CSCs。这些结果提供了使用从肿瘤细胞中胞吐出的仿生仿生纳米颗粒作为有效的癌症化学疗法的有希望的药物载体的概念证明。

更新日期：2019-08-23

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