|Title:||The Role of Adenosine Receptor and Caveolae-Mediated Endocytosis in Oligonucleotide-Mediated Gene Transfer||Authors:||CHUNG, YI-CHEN
|Keywords:||Oligonucleotide;Gene delivery;Adenosine;Endocytosis;Caveolae||Issue Date:||2011||Source:||BIOMATERIALS||Journal Volume:||v.32||Journal Issue:||n.19||Start page/Pages:||4471-4480||Abstract:||
We previously reported the preparation and characterization of ternary nanoparticles with the negative surface charge, which comprises histidine- conjugated polyallylamine (PAA-HIS )/DNA core complex and a single- stranded oligonucleotide outer layer, to transfect various cell lines. As a continued effort, here the investigations on the endocytotic mechanisms involved in the uptake of the oligonucleotide- coated PAA-HIS/DNA complexes are reported. Interestingly, these complexes showed enhanced transfection efficiency only when deoxyadenosine-containing oligonucleotides were deposited on the PAA-HIS/DNA complex surface. The addition of uncomplexed oligonucleotide, free adenosine and adenosine receptor antagonist significantly inhibited the transfection efficiency of oligonucleotide-coated PAA-HIS/ DNA complexes. These results indicated that the oligonucleotide-coated PAA-HIS/DNA complexes could specifically recognize adenosine receptors on the cell surface and were taken up by adenosine receptor-mediated process. Uptake and transfection experiments with various endocytic inhibitors suggested that, after receptor/ligand binding, oligonucleotide-coated PAA-HIS/DNA/complexes were mainly internalized via caveolae-mediated pathway to result in effective intracellular processing for gene expression. In conclusion, both adenosine receptor and caveolae-mediated endocytosis play important roles in oligonucleotide- mediated gene transfer.
|Appears in Collections:||醫學工程學研究所|
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