The softness of tumour-cell-derived microparticles regulates their drug-delivery efficiency

被引:179
作者
Liang, Qingle [1 ]
Bie, Nana [1 ]
Yong, Tuying [1 ]
Tang, Ke [2 ]
Shi, Xiaolong [3 ,4 ]
Wei, Zhaohan [1 ]
Jia, Haibo [5 ]
Zhang, Xiaoqiong [1 ]
Zhao, Haiyan [4 ]
Huang, Wei [1 ]
Gan, Lu [1 ,6 ]
Huang, Bo [2 ,7 ,8 ]
Yang, Xiangliang [1 ,6 ]
机构
[1] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Natl Engn Res Ctr Nanomed, Wuhan, Hubei, Peoples R China
[2] Huazhong Univ Sci & Technol, Tongji Med Coll, Dept Biochem & Mol Biol, Wuhan, Hubei, Peoples R China
[3] Guangzhou Univ, Inst Comp Sci & Technol, Guangzhou, Guangdong, Peoples R China
[4] Huazhong Univ Sci & Technol, Sch Artificial Intelligent & Automat, Wuhan, Hubei, Peoples R China
[5] Huazhong Univ Sci & Technol, Coll Life Sci & Technol, Minist Educ, Key Lab Mol Biophys, Wuhan, Hubei, Peoples R China
[6] Huazhong Univ Sci & Technol, Hubei Key Lab Bioinorgan Chem & Mat Med, Wuhan, Hubei, Peoples R China
[7] Chinese Acad Med Sci, Peking Union Med Coll, Inst Basic Med Sci, Dept Immunol, Beijing, Peoples R China
[8] Chinese Acad Med Sci, Peking Union Med Coll, Inst Basic Med Sci, Natl Key Lab Med Mol Biol, Beijing, Peoples R China
基金
中国国家自然科学基金;
关键词
EXTRACELLULAR VESICLES; REPOPULATING CELLS; ENDOTHELIAL-CELLS; SYSTEMIC TOXICITY; SIDE-POPULATION; CANCER; HYPOXIA; HETEROGENEITY; ACCUMULATION; PHAGOCYTOSIS;
D O I
10.1038/s41551-019-0405-4
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
Extracellular microparticles (MPs) can function as drug-delivery vehicles for anticancer drugs. Here, we show that the softness of MPs derived from tumour-repopulating cells (TRCs) isolated from three-dimensional fibrin gels enhances the MPs' drug-delivery efficiency. We found that, compared with MPs derived from tumour cells cultured in conventional tissue-culture plastic, TRC-derived MPs intravenously injected in tumour-xenograft-bearing mice showed enhanced accumulation in tumour tissues, enhanced blood-vessel crossing and penetration into tumour parenchyma, and preferential uptake by highly tumorigenic TRCs. We also show that the cytoskeleton-related protein cytospin-A plays a critical role in the regulation of TRC-derived MP softness. The modulation of the mechanical properties of TRC-derived MPs could aid the efficiency of delivery of anticancer drugs.
引用
收藏
页码:729 / 740
页数:12
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