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Rho GTPases in A549 and Caco-2 cells dominating the endocytic pathways of nanocarbons with different morphologies

Authors Song S, Fu H, He B, Wang D, Qin M, Yang D, Liu D, Song G, Shi Y, Zhang H, Wang X, Dai W, Zhang Q

Received 7 February 2018

Accepted for publication 24 April 2018

Published 27 July 2018 Volume 2018:13 Pages 4391—4404

DOI https://doi.org/10.2147/IJN.S164866

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Jiang Yang

Peer reviewer comments 3

Editor who approved publication: Dr Linlin Sun


Siyang Song,1,2,* Hongzhe Fu,2,* Bing He,2 Dan Wang,3 Mengmeng Qin,2 Dan Yang,1,2 Dechun Liu,2 Ge Song,2 Yujie Shi,2 Hua Zhang,2 Xueqing Wang,2 Wenbing Dai,2 Qiang Zhang1,2

1School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China; 2Beijing Key Laboratory of Molecular Pharmaceutics and the State Key Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing 100191, China; 3Pharmaceutics Department, Institute of Medicinal Biotechnology, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China

*These authors contributed equally to this work

Introduction: Endocytosis of nanomaterials is the first step of nano-bio interaction and current regulation is mostly by nanomaterials but seldom by intracellular signaling proteins.
Materials and methods: Herein, we synthesized tubular nanocarbon (oxMWCNT) and lamellar-like nanocarbon (oxGRAPHENE) and formulated their aqueous dispersion. A549 and Caco-2 cells were selected as the models of tumor and intestinal epithelial cells, respectively. After knocking down three members of Rho GTPases (Cdc42, Rac1, RhoA) in these two cell lines, their silencing effects on the uptake pathways of nanomaterials with different morphologies were investigated.
Results: An unexpected finding was that the knock-down led to opposite uptake trends in different types of cells. The endocytosis of carbon nanomaterials increased in Caco-2 cells when Rho GTPases were inactivated, while that in A549 cells decreased. For nanomaterials with different shapes, the involved GTPase member of Rho family, or regulating protein molecule, was different. Concretely, Cdc42 and Rac1 were involved in oxMWCNT endocytosis, while all three GTPases participated in oxGRAPHENE internalization. More interestingly, such difference induced different uptake pathways, namely, the cellular uptake of oxMWCNT was clathrin-mediated and oxGRAPHENE was caveolin-modulated, both with the involvement of dynamin.
Conclusion: In conclusion, this study provides new insights for the potential intervention in nano-bio interplay.

Keywords:
shape, cellular uptake, intracellular distribution, nanomaterials, Rho GTPases

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