The microgravity enhanced polymer-mediated siRNA gene silence by improving cellular uptake
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Biophysics Reports
R E S E A RC H A RT I C L E
The microgravity enhanced polymer-mediated siRNA gene silence by improving cellular uptake Tongren Yang1, Chanchan Yu1, Changrong Wang2, Chunhui Li1, Mengjie Zhang1, Xiaofan Luo1, Yuhua Weng1, Anjie Dong2, Xiaoqiong Li1, Yulin Deng1, Yuanyu Huang1,3& 1
2
3
School of Life Science, Advanced Research Institute of Multidisciplinary Science, Institute of Engineering Medicine, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing 100081, China Department of Polymer Science and Technology, School of Chemical Engineering and Technology, Key Laboratory of Systems Bioengineering of the Ministry of Education, Tianjin University, Tianjin 300072, China School of Pharmacy, Hunan University of Chinese Medicine, Changsha 410208, China
Received: 27 June 2020 / Accepted: 18 August 2020 / Published online: 23 November 2020
Graphical abstract Outer frame Inner frame
Drive motor Culture lask 5rmp
5rmp
RPM
50 nmol/L siRNA
siRNA binding
EAASc/siRNA nanomicells
EAASc NPs
Cell culture vessel
ke Upta
pH-respo n disassem sive bly
End o esc some ape
mRNA C RIS ing d a o l
Protein synthesis
mRNA cleavage
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s41048-020-00121-y) contains supplementary material, which is available to authorized users. & Correspondence: [email protected] (Y. Huang)
266 | December 2020 | Volume 6 | Issue 6
Ó The Author(s) 2020
RESEARCH ARTICLE
The effects of microgravity on RNA interference
Abstract
Microgravity (MG) effect is a weightlessness phenomenon caused by the distance from the ground or low gravity of other planets outside the earth’s atmosphere. The various effects of MG have been corroborated in human and animal studies and modeled in cell-based analogs. However, the impact of MG on siRNA performance remains to be elucidated, which is crucial for aerospace medicine. In this study, we prepared nucleic acid nanomicelles (EAASc/siRNA) by using tri-block copolymer of PEG45PAMA40-P(C7A36-DBA37) (EAASc) and siRNA and explored its working mechanism under simulated microgravity (SMG) condition generated by a random positioning machine (RPM). The binding ability of EAASc to siRNA and silence activity were firstly confirmed in normal gravity (NG) environment. Evaluation of PLK1 mRNA expression revealed that gene inhibition efficiencies were increased by 28.7% (HepG2) and 28.9% (A549) under SMG condition, compared with those under NG condition. In addition, mechanism exploration indicated that morphology and migration capability of cancer cells were significantly changed, the internalization of EAASc/siRNA by cells was magnified when the cells were incubated with RPM. No significant difference was observed regarding the expression profiles of genes involved in RNA interference (RNAi) pathway, including Ago2, Dicer, TRBP, and so on. Taken together, siRNA activity was elevated under SMG condition owning to increased cellular internalization. This study, for the first time
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