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Triblock copolymer nanovesicles for pH-responsive targeted delivery and controlled release of siRNA to cancer cells

Gallon, Elena; Matini, Teresa; Sasso, Luana; Mantovani, Giuseppe; Armiñan de Benito, Ana; Sanchis, Joaquin; Caliceti, Paolo; Alexander, Cameron; Vicent, Maria J.; Salmaso, Stefano


Elena Gallon

Teresa Matini

Luana Sasso

Ana Armiñan de Benito

Joaquin Sanchis

Paolo Caliceti

Maria J. Vicent

Stefano Salmaso


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.


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), doi: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
Public URL
Publisher URL
Copyright Statement Copyright information regarding this work can be found at the following address: