Dendritic Poly(l-lysine)-b-Poly(l-lactide)-b-Dendritic Poly(l-lysine) Amphiphilic Gene Delive
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文摘
As an effort to prepare new efficient gene delivery vectors, we have recently developed and reported an amphiphilic dendritic poly(l-lysine)-b-poly(l-lactide)-b-dendritic poly(l-lysine) D2-PLLA-D2 with two-generation PLL dendrons and a PLLA block. In this work, we continued to explore the roles of dendritic PLL generation in DNA binding and intracellular delivery of gene, and a new series of amphiphilic dendritic poly(l-lysine)-b-poly(l-lactide)-b-dendritic poly(l-lysine)s Dn-PLLA-Dn (n = 3−5) were synthesized and were structurally characterized. Furthermore, plasmid DNA binding affinity for these cationic amphiphiles was examined by agarose gel electrophoresis and fluorescence titration assay in pure water and PBS buffer solution containing 150 mM NaCl (pH = 7.4), respectively. By dynamic light scattering (DLS) and transmission electronic microscopy (TEM), the interaction and complexation in between were investigated, concerning the DNA/vector polyplex particle morphologies and zeta potentials. Utilizing a human hepatocellular carcinoma cell-line SMMC-7721, cell toxicity, and gene transfection in vitro were explored. To further improve transgene efficiency for these synthetic cationic amphiphiles as gene delivery vectors, new structural DEn-PLLA-DEn (n = 2−3) were prepared through an amino termini modification of the Dn-PLLA-Dn (n = 2−3) with less toxic 4,7,10,13-tetraazatridecanoic acids, and gene transfection with these DEn-PLLA-DEn (n = 2−3) was examined with an alternative human gastric carcinoma cell-line HGC-27. As a result, the high plasmid DNA binding affinity, low cytotoxicity, and much enhanced transgene efficacy suggest a new possible clue to design effective synthetic gene delivery vectors with amphiphilic skeleton and less toxic polyamine building blocks.

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