Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0267964 (PAA)
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Ternary nanoparticles with negatively charged surface were prepared by coating single-stranded oligonucleotides (5'-C(10)A(20)-3') on histidine-conjugated polyallylamine (PAA-HIS)/DNA complexes for gene delivery. Characterization of PAA-HIS/DNA/oligonucleotide complexes demonstrated that nanoparticles possessed the negative surface charge -27 mV and size of around 100 nm when the molar ratio of oligonucleotide/PAA-HIS exceeded 1.5. The negatively charged oligonucleotide-coated PAA-HIS/DNA complexes could be entirely internalized by the living HeLa cells to exhibit high gene expression with low cytotoxicity and the resistance against erythrocyte agglutination and serum inhibition. Since the gene expression of PAA-HIS/DNA complexes was significantly inhibited by coating other polyanions and oligonucleotides, the ternary PAA-HIS/DNA/deoxyadenosine-rich oligonucleotide complexes were uptaken by specific receptor-mediated process. Additionally, the deposition of a layer of oligonucleotides onto the binary PAA-HIS/DNA complexes could effectively transfect various types of cells including HEK-293, HepG2 and Hs68 cells, indicating the technology of coating specific oligonucleotides on PAA-HIS/DNA complexes or other cationic binary DNA complexes might facilitate the use of nanoparticles for safe and efficient gene delivery and eventual therapy.
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PMID:Polycation/DNA complexes coated with oligonucleotides for gene delivery. 2016 54

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.
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PMID:The role of adenosine receptor and caveolae-mediated endocytosis in oligonucleotide-mediated gene transfer. 2144 Feb 94