Nanoparticulates reduce tumor cell migration through affinity interactions with extracellular migrasomes and retraction fibers

被引：22

作者：

Cheng, Yuxi ^{[1
,2
]}

Ren, Junji ^{[1
,2
]}

Fan, Shumin ^{[1
,2
]}

Wu, Peiyao ^{[1
,2
,3
]}

Cong, Wenshu ^{[1
,2
]}

Lin, Yuxing ^{[1
,2
]}

Lan, Shaojie ^{[1
,2
]}

Song, Siyang ^{[1
,2
]}

Shao, Bin ^{[4
]}

Dai, Wenbing ^{[1
,2
]}

Wang, Xueqing ^{[1
,2
]}

Zhang, Hua ^{[1
,2
]}

Xu, Bo ^{[2
]}

Li, Wenzhe ^{[2
]}

Yuan, Xia ^{[2
]}

He, Bing ^{[1
,2
]}

Zhang, Qiang ^{[1
,2
,3
]}

机构：

[1] Peking Univ, Sch Pharmaceut Sci, Beijing Key Lab Mol Pharmaceut & New Drug Deliver, Beijing 100191, Peoples R China

[2] Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

[3] Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Peoples R China

[4] Peking Univ, Canc Hosp, Key Lab Carcinogenesis & Translat Res, Minist Educ,Dept Med Oncol, Beijing 100142, Peoples R China

来源：

NANOSCALE HORIZONS | 2022年 / 7卷 / 07期

基金：

中国国家自然科学基金;

关键词：

DRUG-DELIVERY; ADHESION; INVASION; SURFACE; MECHANISMS; TRANSPORT; PEPTIDE; ECM;

D O I：

10.1039/d2nh00067a

中图分类号：

O64 [物理化学（理论化学）、化学物理学];

学科分类号：

070304 ; 081704 ;

摘要：

Nano-tumor interactions are fundamental for cancer nanotherapy, and the cross-talk of nanomedicines with the extracellular matrix (ECM) is increasingly considered essential. Here, we specifically investigate the nano-ECM interactivity using drug-free nanoparticulates (NPs) and highly metastatic cancer cells as models. We discover with surprise that NPs closely bind to specific types of ECM components, namely, retraction fibers (RFs) and migrasomes, which are located at the rear of tumor cells during their migration. This interaction is observed to alter cell morphology, limit cell motion range and change cell adhesion. Importantly, NPs are demonstrated to inhibit tumor cell removal in vitro, and their anti-metastasis potential is preliminarily confirmed in vivo. Mechanically, the NPs are found to coat and form a rigid shell on the surface of migrasomes and retraction fibers via interaction with lipid raft/caveolae substructures. In this way, NPs block the recognition, endocytosis and elimination of migrasomes by their surrounding tumor cells. Thereby, NPs interfere with the cell-ECM interaction and reduce the promotion effect of migrasomes on cell movement. Additionally, NPs trigger alteration of the expression of proteins related to cell-cell adhesion and cytoskeleton organization, which also restricts cell migration. In summary, all the findings here provide a potential target for anti-tumor metastasis nanomedicines.

引用

页码：779 / 789

页数：11

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[11] Particle Targeting in Complex Biological Media [J].