Amphoteric hyaluronic acid derivative for targeting gene delivery.
The study aimed to develop an amphoteric hyaluronic acid (HA) derivative with polyethyleneimine (PEI) chains (HAP) for gene delivery to overcome the disadvantages of PEI as gene carrier including the cytotoxicity caused by excess of positive charge, non-special interaction and aggregation in the blood, and non-target gene delivery. The HAP was synthesized by an imine reaction between periodate-oxidized HA and PEI. The HAP/DNA complex was prepared, and its characterization was investigated. The size of complex with higher molecular weight HA in PBS was about 200 nm at optimal charge ratio. No apparent aggregation among the particles was observed. The HAPs also showed high protection of DNA from nuclease, better dissociation of DNA from the complex and lower cytotoxicity. It also exhibited higher transfection efficiency in HepG2 cells than the PEI/DNA complex. Among all complexes, the HAP50/DNA complex was especially found to be most efficient, yielding comparable transfection efficiency with that of Lipofectamine/DNA lipoplexes. Moreover, the HAP-IR820 obviously accumulated in tumor after i.v. administration as compared to the PEI-IR820, which indicated that the HAP could assist the DNA targeting to the tumor. Therefore, HAP should be a promising non-viral gene vector.
Yao
Jing
J
Department of pharmaceutics, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, China. yaoj3@163.com
Fan
Ying
Y
Du
Ronghui
R
Zhou
Jianping
J
Lu
Yun
Y
Wang
Wei
W
Ren
Jin
J
Sun
Xiaojing
X
D000818:Animals; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry; D018014:Gene Transfer Techniques; D056945:Hep G2 Cells; D006801:Humans; D006820:Hyaluronic Acid / Q000031:analogs & derivatives*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D011094:Polyethyleneimine / Q000737:chemistry; D014162:Transfection
D011094:Polyethyleneimine; D006820:Hyaluronic Acid; D004247:DNA