Effective tolerance to serum proteins of head-tail type polycation vectors by PEGylation at the periphery of the head block.
To improve the stability of a head-tail type polycation (PAMAM dendron-PLL), which is composed of a polyamidoamine (PAMAM) dendron head and poly(l-lysine) (PLL) tail blocks, as a gene vector against serum proteins, the PEGylation of the PAMAM dendron head was examined using physicochemical and transfection experiments. The PEGylation of the PAMAM dendron-PLL polyplexes neutralized the zeta-potential, indicating that the PEG brushes surround the surface of the polyplexes. The PEGylated PAMAM dendron-PLL polyplexes had higher tolerance against incubation with serum proteins when compared with non-PEGylated PAMAM dendron-PLL polyplexes. In addition, the transfection efficiency of the PEGylated PAMAM dendron-PLL polyplexes increased with increasing incubation periods, leading to an increase in the amount of pDNA uptaked by HeLa cells. Furthermore, effective stabilization of the PAMAM dendron-PLL polyplexes through PEGylation of the PAMAM dendron block was confirmed by the transfection experiments after preincubation with serum proteins and the PEGylated PAMAM dendron-PLL polyplexes showed a comparable level of transfection efficiency with polyethyleneimine polyplexes.
Harada
Atsushi
A
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, 1-1 Gakuen-cho, Naka-ku, Sakai, Osaka 599-8531, Japan. harada@chem.osakafu-u.ac.jp
Kimura
Yuka
Y
Kojima
Chie
C
Kono
Kenji
K
D001672:Biocompatible Materials / Q000737:chemistry*; D001798:Blood Proteins / Q000737:chemistry / Q000378:metabolism*; D004247:DNA / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D050091:Dendrimers / Q000737:chemistry*; D005822:Genetic Vectors / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D018625:Microscopy, Atomic Force; D011073:Polyamines / Q000737:chemistry; D000071228:Polyelectrolytes; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry*; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D014162:Transfection
D001672:Biocompatible Materials; D001798:Blood Proteins; D004247:DNA; D050091:Dendrimers; D011073:Polyamines; D000071228:Polyelectrolytes; D011092:Polyethylene Glycols; D011094:Polyethyleneimine; D011107:Polylysine; D011108:Polymers; C104700:PAMAM Starburst