A spermine conjugated stearic acid-g-chitosan oligosaccharide polymer with different types of amino groups for efficient p53 gene therapy.
The effect of various amino groups on gene vector is different. In order to combine their effect in one vector and finally promote the transfection efficiency, a biogenic tetra-amine spermine was introduced to modify the stearic acid-grafted chitosan oligosaccharide (CSOSA) polymer to build a new gene delivery system. The spermine linked CSOSA (SP-CSOSA) polymer consists two types of amino groups with 73.3%, 19.3% of all nitrogen atoms for primary and secondary amine groups, respectively. The SP modified CSOSA showed strong DNA condensation capability and obviously enhanced proton binding ability especially at about pH 5.0, which significantly promoted the escape of SP-CSOSA/pDNA complexes from endo-lysosoms. Moreover, the transfection efficiency at the N/P ratio of 10 could compete with that of Lipofectamine 2000 and PEI 25K, but with lower cytotoxicities. The therapeutic wild type p53 gene transfected by the SP-CSOSA polymer restored the function of aberrant p53 gene and induced obvious cell apoptosis and G1 phase arrest. We concluded that the new vector SP-CSOSA polymer proved to be a potential delivery system for gene therapy.
College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, People's Republic of China.
Tingting
T
Meng
College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, People's Republic of China.
Jie
J
Wu
College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, People's Republic of China.
Hanxi
H
Yi
College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, People's Republic of China.
Jingwen
J
Liu
College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, People's Republic of China.
Binbin
B
Lu
College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, People's Republic of China.
Ming
M
Yuan
Department of Pharmacy, School of Medicine Science, Jiaxing University, Zhejiang 314001, People's Republic of China.
Xuan
X
Huang
College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, People's Republic of China.
Hong
H
Yuan
College of Pharmaceutical Science, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, People's Republic of China. Electronic address: hufq@zju.edu.cn.
Fuqiang
F
Hu
D048271:Chitosan / Q000737:chemistry*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D011108:Polymers / Q000737:chemistry*; D013096:Spermine / Q000737:chemistry*; D013229:Stearic Acids / Q000737:chemistry*; D014162:Transfection / Q000379:methods; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics
D011108:Polymers; D013229:Stearic Acids; D016159:Tumor Suppressor Protein p53; D013096:Spermine; C031183:stearic acid; D048271:Chitosan
Endo-lysosomal escape; Gene delivery system; Spermine; Transfection efficiency; p53 Gene therapy