Properties and Evaluation of Quaternized Chitosan/Lipid Cation Polymeric Liposomes for Cancer-Targeted Gene Delivery

• Published in: Langmuir 2013-07, Vol.29 (27), p.8683-8693
• Main Authors: Liang, Xiaofei, Li, Xiaoyu, Chang, Jin, Duan, Yourong, Li, Zonghai
• Format: Article
• Language: English
• Subjects: Animals; Cations - chemistry; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival - drug effects; Chemistry; Chitosan - chemistry; Colloidal state and disperse state; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Exact sciences and technology; Female; Gene Transfer Techniques; General and physical chemistry; Genetic Vectors - chemical synthesis; Genetic Vectors - chemistry; Genetic Vectors - pharmacology; Hep G2 Cells; Humans; Lipids - chemistry; Liposomes - chemical synthesis; Liposomes - chemistry; Liposomes - pharmacology; Membranes; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasms - drug therapy; Neoplasms - pathology; Particle Size; Polymers - chemistry; Structure-Activity Relationship; Surface Properties
• ISSN: 0743-7463; 1520-5827
• DOI: 10.1021/la401166v

Development of high-stability and efficient nonviral vectors with low cytoxicity is important for targeted tumor gene therapy. In this study, cationic polymeric liposomes (CPLs), with similar lipid bilayer structure and high thermal stability, were prepared from polymeric surfactants of quaternized (carboxymethyl)chitosan with different carbon chains (dodecyl, tetradecyl, hexadecyl, and octadecyl). By comparing different factors that influence gene delivery, tetradecyl-quaternized (carboxymethy)chitosan (TQCMC) CPLs, with suitable size (184.4 ± 17.1 nm), ζ potentials (27.5 ± 4.9 mV), and productivity for synthesis TQCMC (weight yield 13.1%), were selected for gene transfection evaluation in various cancer cell lines. Although TQCMC CPLs have lower gene transfection efficiency compared with cationic liposomes (Lipofectamine 2000) in vitro, they displayed higher reporter gene delivery ability for cancer tissues (bearing U87 and SMMC-7721 tumors) in vivo after intravenous injection. TQCMC CPLs also have lower cell cytotoxicity and lower cytokine production or liver injury for BALB/c mice. We conclude that the CPLs are promising gene delivery systems that may be used to target various cancers.