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Int. J. Mol. Sci. 2014, 15(11), 20339-20354; doi:10.3390/ijms151120339

α, ω-Cholesterol-Functionalized Low Molecular Weight Polyethylene Glycol as a Novel Modifier of Cationic Liposomes for Gene Delivery

1
Department of Anesthesiology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China
2
Central Laboratory, Science Education Department, Chengdu Normal University, Chengdu 610041, Sichuan, China
3
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA
These authors contributed equally to this work.
*
Authors to whom correspondence should be addressed.
Received: 28 August 2014 / Revised: 25 September 2014 / Accepted: 30 September 2014 / Published: 6 November 2014
(This article belongs to the Section Biomaterial Sciences)
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Abstract

Here, three novel cholesterol (Ch)/low molecular weight polyethylene glycol (PEG) conjugates, termed α, ω-cholesterol-functionalized PEG (Ch2-PEGn), were successfully synthesized using three kinds of PEG with different average molecular weight (PEG600, PEG1000 and PEG2000). The purpose of the study was to investigate the potential application of novel cationic liposomes (Ch2-PEGn-CLs) containing Ch2-PEGn in gene delivery. The introduction of Ch2-PEGn affected both the particle size and zeta potential of cationic liposomes. Ch2-PEG2000 effectively compressed liposomal particles and Ch2-PEG2000-CLs were of the smallest size. Ch2-PEG1000 and Ch2-PEG2000 significantly decreased zeta potentials of Ch2-PEGn-CLs, while Ch2-PEG600 did not alter the zeta potential due to the short PEG chain. Moreover, the in vitro gene transfection efficiencies mediated by different Ch2-PEGn-CLs also differed, in which Ch2-PEG600-CLs achieved the strongest GFP expression than Ch2-PEG1000-CLs and Ch2-PEG2000-CLs in SKOV-3 cells. The gene delivery efficacy of Ch2-PEGn-CLs was further examined by addition of a targeting moiety (folate ligand) in both folate-receptor (FR) overexpressing SKOV-3 cells and A549 cells with low expression of FR. For Ch2-PEG1000-CLs and Ch2-PEG2000-CLs, higher molar ratios of folate ligand resulted in enhanced transfection efficacies, but Ch2-PEG600-CLs had no similar in contrast. Additionally, MTT assay proved the reduced cytotoxicities of cationic liposomes after modification by Ch2-PEGn. These findings provide important insights into the effects of Ch2-PEGn on cationic liposomes for delivering genes, which would be beneficial for the development of Ch2-PEGn-CLs-based gene delivery system. View Full-Text
Keywords: cholesterol; polyethylene glycol; cationic liposomes; gene delivery; folate ligand cholesterol; polyethylene glycol; cationic liposomes; gene delivery; folate ligand
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MDPI and ACS Style

Ma, C.-C.; He, Z.-Y.; Xia, S.; Ren, K.; Hui, L.-W.; Qin, H.-X.; Tang, M.-H.; Zeng, J.; Song, X.-R. α, ω-Cholesterol-Functionalized Low Molecular Weight Polyethylene Glycol as a Novel Modifier of Cationic Liposomes for Gene Delivery. Int. J. Mol. Sci. 2014, 15, 20339-20354.

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