Redox-sensitive, cholesterol-bearing PEGylated poly(propyleneimine)-based dendrimersomes for drug and gene delivery to cancer cells
Laskar, Partha and Somani, Sukrut and Altwaijry, Najla Abdullah S and Mullin, Margaret and Bowering, Deborah and Warzecha, Monika and Keating, Patricia and Tate, Rothwelle J. and Leung, Hing Y. and Dufès, Christine (2018) Redox-sensitive, cholesterol-bearing PEGylated poly(propyleneimine)-based dendrimersomes for drug and gene delivery to cancer cells. Nanoscale, 10 (48). pp. 22830-22847. ISSN 2040-3372
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Abstract
Stimuli-responsive nanocarriers have attracted increasing attention for drug and gene delivery in cancer therapy. The present study reports the development of redox-sensitive dendrimersomes made of disulphide-linked cholesterol-bearing PEGylated dendrimers, that can be used as drug and gene delivery systems. Two disulphide-linked cholesterol-bearing PEGylated generation 3-diaminobutyric polypropylenimine dendrimers have been successfully synthesized through in situ two-step reaction. They were able to spontaneously self-assemble into stable, cationic, nanosized vesicles (or dendrimersomes), with lower critical aggregation concentration values for high cholesterol-bearing vesicles. These dendrimersomes were able to entrap both hydrophilic and hydrophobic dyes, and also showed a redox-responsive sustained release of the entrapped guests in presence of a glutathione concentration similar to that of the cytosolic reducing environment. The high cholesterol-bearing dendrimersome was found to have a higher melting enthalpy, an increased adsorption tendency on mica surface, was able to entrap a larger amount of hydrophobic drug and was more resistant to redox-responsive environment in comparison with its low cholesterol counterpart. In addition, both dendrimersomes were able to condense more than 85% of the DNA at all tested ratios for the low-cholesterol vesicles, and at dendrimer: DNA weight ratios of 1:1 and higher for the high-cholesterol vesicles. These vesicles resulted in an enhanced cellular uptake of DNA, by up to 15-fold compared with naked DNA with the low-cholesterol vesicles. As a result, they increased gene transfection on PC-3 prostate cancer cell line, with the highest transfection being obtained with low-cholesterol vesicle complex at a dendrimer: DNA weight ratio of 5:1 and high-cholesterol vesicle complex at a dendrimer: DNA weight ratio of 10:1. These transfection levels were about 5-fold higher than that observed when treated with DNA. These cholesterol-bearing PEGylated dendrimer-based vesicles are therefore promising as redox-sensitive drug and gene delivery systems for potential applications in combination cancer therapy.
Creators(s): |
Laskar, Partha, Somani, Sukrut ![]() ![]() ![]() ![]() ![]() | Item type: | Article |
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ID code: | 65993 |
Keywords: | dendrimer, polyethylene glycol, cholesterol, redox sensitivity, gene delivery, drug delivery, atomic force microscopy, Therapeutics. Pharmacology, Pharmacology (medical) |
Subjects: | Medicine > Therapeutics. Pharmacology |
Department: | Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences Faculty of Science > Pure and Applied Chemistry Technology and Innovation Centre > Bionanotechnology |
Depositing user: | Pure Administrator |
Date deposited: | 06 Nov 2018 10:12 |
Last modified: | 24 Jan 2021 03:22 |
Related URLs: | |
URI: | https://strathprints.strath.ac.uk/id/eprint/65993 |
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