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

International Journal of Molecular Sciences

Cui-Cui Ma¹  Zhi-Yao He¹  Shan Xia¹  Ke Ren²  Li-Wei Hui¹  Han-Xiao Qin¹  Ming-Hai Tang¹  Jun Zeng¹  Xiang-Rong Song¹ 

[1] Department of Anesthesiology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; E-Mails:;Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, NE 68198, USA; E-Mail:

关键词: cholesterol;    polyethylene glycol;    cationic liposomes;    gene delivery;    folate ligand;   

DOI  :  10.3390/ijms151120339

来源: mdpi

【 摘 要 】

Here, three novel cholesterol (Ch)/low molecular weight polyethylene glycol (PEG) conjugates, termed α, ω-cholesterol-functionalized PEG (Ch₂-PEG_n), 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-PEG_n-CLs) containing Ch₂-PEG_n in gene delivery. The introduction of Ch₂-PEG_n 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-PEG_n-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-PEG_n-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-PEG_n-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-PEG_n. These findings provide important insights into the effects of Ch₂-PEG_n on cationic liposomes for delivering genes, which would be beneficial for the development of Ch₂-PEG_n-CLs-based gene delivery system.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.