Octadecyl chain-bearing PEGylated poly(propyleneimine)-based dendrimersomes: physicochemical studies, redox-responsiveness, DNA condensation, cytotoxicity and gene delivery to cancer cells

Laskar, P., Somani, S., Mullin, M., Tate, R. J., Warzecha, M., Bowering, D., Keating, P., Irving, C., Leung, H. Y. and Dufès, C. (2021) Octadecyl chain-bearing PEGylated poly(propyleneimine)-based dendrimersomes: physicochemical studies, redox-responsiveness, DNA condensation, cytotoxicity and gene delivery to cancer cells. Biomaterials Science, 9(4), pp. 1431-1448. (doi: 10.1039/D0BM01441A) (PMID:33404026)

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Abstract

Stimuli-responsive nanocarriers have become increasingly important for nucleic acid and drug delivery in cancer therapy. Here, we report the synthesis, characterization and evaluation of disulphide-linked, octadecyl (C18 alkyl) chain-bearing PEGylated generation 3-diaminobutyric polypropylenimine dendrimer-based vesicles (or dendrimersomes) for gene delivery. The lipid-bearing PEGylated dendrimer was successfully synthesized through in situ two-step reaction. It was able to spontaneously self-assemble into stable, cationic, nanosized vesicles, with low critical aggregation concentration value, and also showed redox-responsiveness in presence of a glutathione concentration similar to that of the cytosolic reducing environment. In addition, it was able to condense more than 70% of DNA at dendrimer: DNA weight ratios of 5 : 1 and higher. This dendriplex resulted in an enhanced cellular uptake of DNA at dendrimer: DNA weight ratios of 10 : 1 and 20 : 1, by up to 16-fold and by up to 28-fold compared with naked DNA in PC-3 and DU145 prostate cancer cell lines respectively. At a dendrimer: DNA weight ratio of 20 : 1, it led to an increase in gene expression in PC-3 and DU145 cells, compared with DAB dendriplex. These octadecyl chain-bearing, PEGylated dendrimer-based vesicles are therefore promising redox-sensitive drug and gene delivery systems for potential applications in combination cancer therapy.

Item Type:Articles
Additional Information:This work was financially supported by a grant from Worldwide Cancer Research [grant number 16-1303] to C. D. and H. Y. L. P. L. and S.S. are respectively funded by research grants from Worldwide Cancer Research [grant number 16-1303] and The Dunhill Medical Trust [grant number R463/0216].
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Leung, Professor Hing and Mullin, Mrs Margaret
Authors: Laskar, P., Somani, S., Mullin, M., Tate, R. J., Warzecha, M., Bowering, D., Keating, P., Irving, C., Leung, H. Y., and Dufès, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Biomaterials Science
Publisher:Royal Society of Chemistry
ISSN:2047-4830
ISSN (Online):2047-4849
Published Online:22 December 2020

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