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

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Laskar, Partha and Somani, Sukrut and Mullin, Margaret and Tate, Rothwelle and Warzecha, Monika and Bowering, Deborah and Keating, Patricia and Irving, Craig and Leung, Hing Y and Dufès, Christine (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. ISSN 2047-4830 (https://doi.org/10.1039/d0bm01441a)

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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. This journal is

ORCID iDs

Laskar, Partha, Somani, Sukrut ORCID logoORCID: https://orcid.org/0000-0002-0697-1110, Mullin, Margaret, Tate, Rothwelle, Warzecha, Monika ORCID logoORCID: https://orcid.org/0000-0001-6166-1089, Bowering, Deborah ORCID logoORCID: https://orcid.org/0000-0002-8934-3469, Keating, Patricia, Irving, Craig, Leung, Hing Y and Dufès, Christine ORCID logoORCID: https://orcid.org/0000-0002-7963-6364;
CORE (COnnecting REpositories)