Elena Gallon
Triblock copolymer nanovesicles for pH-responsive targeted delivery and controlled release of siRNA to cancer cells
Gallon, Elena; Matini, Teresa; Sasso, Luana; Mantovani, Giuseppe; Armi�an de Benito, Ana; Sanchis, Joaquin; Caliceti, Paolo; Alexander, Cameron; Vicent, Maria J.; Salmaso, Stefano
Authors
Teresa Matini
Luana Sasso
GIUSEPPE MANTOVANI giuseppe.mantovani@nottingham.ac.uk
Associate Professor
Ana Armi�an de Benito
Joaquin Sanchis
Paolo Caliceti
Professor CAMERON ALEXANDER CAMERON.ALEXANDER@NOTTINGHAM.AC.UK
Professor of Polymer Therapeutics
Maria J. Vicent
Stefano Salmaso
Abstract
New pH-responsive polymersomes for active anticancer oligonucleotide delivery were prepared from triblock copolymers. The delivery systems were formed by two terminal hydrophilic blocks, PEG and polyglycerolmethacrylate (poly-GMA), and a central weakly basic block, polyimidazole-hexyl methacrylate (poly-ImHeMA), which can complex with oligonucleotides and control vesicle formation/disassembly via pH variations. Targeted polymersomes were prepared by mixing folate-derivatized and underivatized copolymers. At pH 5, ds-DNA was found to complex with the pH-responsive copolymers at a N/P molar ratio above ∼2:1, which assisted the encapsulation of ds-DNA in the polymersomes, while low association was observed at pH 7.4. Cytotoxicity studies performed on folate receptor overexpressing KB and B16–F10 cells and low folate receptor expressing MCF-7 cells showed high tolerance of the polymersomes at up to 3 mg/mL concentration. Studies performed with red blood cells showed that at pH 5.0 the polymersomes have endosomolytic properties. Cytofluorimetric studies showed a 5.5-fold higher uptake of ds-DNA loaded folate-functional polymersomes in KB cells compared to nontargeted polymersomes. In addition, ds-DNA was found to be localized both in the nucleus and in the cytosol. The incubation of luciferase transfected B16–F10 cells with targeted polymersomes loaded with luciferase and Hsp90 expression silencing siRNAs yielded 31 and 23% knockdown in target protein expression, respectively.
Citation
Gallon, E., Matini, T., Sasso, L., Mantovani, G., Armiñan de Benito, A., Sanchis, J., …Salmaso, S. (2015). Triblock copolymer nanovesicles for pH-responsive targeted delivery and controlled release of siRNA to cancer cells. Biomacromolecules, 16(7), https://doi.org/10.1021/acs.biomac.5b00286
Journal Article Type | Article |
---|---|
Acceptance Date | Mar 2, 2015 |
Online Publication Date | May 19, 2015 |
Publication Date | Jul 13, 2015 |
Deposit Date | Dec 1, 2016 |
Journal | Biomacromolecules |
Print ISSN | 1525-7797 |
Electronic ISSN | 1526-4602 |
Publisher | American Chemical Society |
Peer Reviewed | Peer Reviewed |
Volume | 16 |
Issue | 7 |
DOI | https://doi.org/10.1021/acs.biomac.5b00286 |
Public URL | https://nottingham-repository.worktribe.com/output/757133 |
Publisher URL | http://dx.doi.org/10.1021/acs.biomac.5b00286 |
Contract Date | Dec 1, 2016 |
You might also like
New biomaterials from renewable resources – amphiphilic block copolymers from δ-decalactone
(2015)
Journal Article
Downloadable Citations
About Repository@Nottingham
Administrator e-mail: discovery-access-systems@nottingham.ac.uk
This application uses the following open-source libraries:
SheetJS Community Edition
Apache License Version 2.0 (http://www.apache.org/licenses/)
PDF.js
Apache License Version 2.0 (http://www.apache.org/licenses/)
Font Awesome
SIL OFL 1.1 (http://scripts.sil.org/OFL)
MIT License (http://opensource.org/licenses/mit-license.html)
CC BY 3.0 ( http://creativecommons.org/licenses/by/3.0/)
Powered by Worktribe © 2024
Advanced Search