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Internalization Characterization of Si Nanorod with Camouflaged Cell Membrane Proteins Reveals ATXN2 as a Negative Regulator

by 1,2,†, 2,3,4,†, 2, 1, 2 and 2,*
1
State Key Laboratory of Pharmaceutical Biotechnology and Ministry of Education Key Laboratory of Model Animals for Disease Study, Model Animal Research Center of Nanjing University, Nanjing 210061, China
2
School of Physical Science and Technology, ShanghaiTech University, 393 Middle Huaxia Road, Shanghai 201210, China
3
Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai 200050, China
4
University of Chinese Academy of Sciences, Beijing 100049, China
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Cells 2019, 8(8), 931; https://doi.org/10.3390/cells8080931
Received: 1 July 2019 / Revised: 14 August 2019 / Accepted: 16 August 2019 / Published: 19 August 2019
The fabrication of shape-controlled nanocarriers is critical for efficient delivery of biomolecules across the cell membrane. Surface coating of the nanocarrier can improve internalization efficiency. Here, we developed a facile method of silicon nanorod fabrication leading to a controlled size and shape. We then systematically evaluated five surface modifications with membrane proteins from different cancer cell lines including MCF7, MD231, Hela, Panc-PDX, and Panc-1. We demonstrated that silicon nanorods coated with either a homolytic or heterolytic membrane protein coating have significantly improved internalization efficiency as compared with uncoated Si nanorods. To elucidate the molecular mechanism of the improved efficiency associated with a modified coating, we analyzed the coating membrane proteins derived from five cell lines with proteomics and identified 601 proteins shared by different cell sources. These proteins may function as cell-substrate adhesion molecules that contribute to the enhanced internalization. We also tested the internalization efficiency of nanorods with different coatings in each of the five cell lines to determine the influencing factors from target cells. We found that the internalization efficiency varied among different target cells, and the ranking of the average efficiency was as follows: Hela > Panc-PDX > MD231 > MCF7 > Panc-1. The bioinformatics analysis suggested that the low internalization efficiency in Panc-1 cells might be associated with the upregulation of ATXN2, which is a negative regulator of endocytosis. We further demonstrated that ATXN2 knockdown with specific siRNA significantly improved nanorod internalization efficiency in Panc-1 cells suggesting that ATXN2 can be a reference for efficiency prediction of nanoparticle delivery to tumor cells. Thus, we studied the effect of different cancer cell membrane proteins on nanorod uptake efficiencies. These results can improve nanorod internalization to cancer cells, including a fundamental understanding of the internalization efficiency of cancer cells. View Full-Text
Keywords: silicon nanorod; cell membrane proteins; cancer; internalization; efficiency; ATXN2 silicon nanorod; cell membrane proteins; cancer; internalization; efficiency; ATXN2
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MDPI and ACS Style

Lu, Y.; Dai, J.; Kong, N.; Liu, J.; Gong, J.; Yao, Y. Internalization Characterization of Si Nanorod with Camouflaged Cell Membrane Proteins Reveals ATXN2 as a Negative Regulator. Cells 2019, 8, 931.

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