a.Zhejiang Key Laboratory of Smart Biomaterials and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou 310027, China
b.Department of Cell Biology, School of Basic Medical Sciences, Zhejiang University, Hangzhou 310058, China
c.The Forth Affiliated Hospital, Zhejiang University School of Medicine, Yiwu 322000, China
d.Hangzhou Global Scientific and Technological Innovation Center, Hangzhou 311215, China
shenyq@zju.edu.cn
收稿:2022-03-08,
修回:2022-04-03,
录用:2022-04-15,
网络首发:2022-07-04,
纸质出版:2022-09-01
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Zhou, Q.; Li, X.; Xiang, J. J.; Shen, Y. Q. Tuning the stability of the polyplex nanovesicles of oligonucleotides via a zinc(II)-coordinative strategy. Chinese J. Polym. Sci. 2022, 40, 1034–1042
Quan Zhou, Xiang Li, Jia-Jia Xiang, et al. Tuning the Stability of the Polyplex Nanovesicles of Oligonucleotides
Zhou, Q.; Li, X.; Xiang, J. J.; Shen, Y. Q. Tuning the stability of the polyplex nanovesicles of oligonucleotides via a zinc(II)-coordinative strategy. Chinese J. Polym. Sci. 2022, 40, 1034–1042 DOI: 10.1007/s10118-022-2764-7.
Quan Zhou, Xiang Li, Jia-Jia Xiang, et al. Tuning the Stability of the Polyplex Nanovesicles of Oligonucleotides
we here report a new methodology for tuning the saline stabilities of polyplex nanovesicles of oligonucleotides by modifying the polycation with Zinc (II)-coordinative cationic chains.
Oligonucleotide therapeutics have great potential to target the currently undruggable genes and to generate entirely new therapeutic paradigms in multiple types of disease
thus having attracted much attention in recent years. However
their applications are greatly hindered by a lack of safe and efficient oligonucleotide-delivery vectors. Polyplex nanovesicles formed from oligonucleotides and the cationic block have shown exceptional features for the delivery of therapeutic oligonucleotides and other biopharmaceuticals. Nevertheless
these polyplex nanovesicles are deeply fraught with difficulty in tolerating physiological ionic strength. Inspired by the high binding ability between the dipicolylamine (DPA)/zinc(II) complex and the phosphodiester moieties of oligonucleotides
herein
we designed a coordinative cationic block to solve the intrinsic stability dilemma. Moreover
we found the stability of the resulted polyplex nanovesicles could be easily tuned by the content of coordinated zinc ions.
In vitro
cellular studies implied that the prepared zinc(II)-coordinative polyplex nanovesicles preferred to retain in the lysosomes upon internalization
making them ideal delivery candidates for the lysosome-targeting oligonucleotide therapeutics.
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