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 > School of Cancer Sciences College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| 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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