Complexes containing cationic and anionic pH-sensitive liposomes: comparative study of factors influencing plasmid DNA gene delivery to tumors
Received 15 January 2013
Accepted for publication 12 March 2013
Published 22 April 2013 Volume 2013:8(1) Pages 1573—1593
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Yan Chen,* Ji Sun,* Ying Lu, Chun Tao, Jingbin Huang, He Zhang, Yuan Yu, Hao Zou, Jing Gao, Yanqiang Zhong
Department of Pharmaceutical Science, School of Pharmacy, The Second Military Medical University, Shanghai, People’s Republic of China
*These authors contributed equally to this work
Abstract: pH-sensitive liposomes represent an effective gene vector in cancer therapy. However, their use is greatly hampered by their relatively low transfection efficiency. To improve the transfection efficiency of pH-sensitive liposomes, we prepared complexes containing 3β-[N-(N',N'-dimethylaminoethane) carbamoyl] cholesterol (DC-Chol) and dioleoylphosphatidyl ethanolamine (DOPE) liposomes and pH-sensitive liposomes composed of cholesteryl hemisuccinate (CHEMS) and DOPE, and evaluated the influence of various factors on plasmid DNA (pDNA) transfection efficiency. All DC-Chol/DOPE liposome/pDNA and pH-sensitive liposome complexes showed similarly potent pH sensitivity. In the presence of serum-containing medium, two optimized complexes of DC-Chol/DOPE liposomes/pDNA and pH-sensitive PEGylated liposomes showed high transfection efficiency of 22.94% and 20.07%, respectively. Notably, DC-Chol/DOPE (2:3) liposomes/pH-sensitive PEGylated (1%) liposome complexes with a charge ratio of 1:1 (m/m [+/-]) showed enhanced accumulation in tumors in vivo. Our results show the influence of various factors on pDNA transfection efficiency in complexes of DC-Chol/DOPE liposomes and pH-sensitive PEGylated liposomes. Understanding of such mechanisms will lead to better design of complexes of DC-Chol/DOPE liposomes and pH-sensitive liposomes for gene therapy.
Keywords: cationic liposomes, pH-sensitive liposomes, pDNA, transfection, PEGylated
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