Polycation/DNA complexes coated with oligonucleotides for gene delivery.
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.
Chung
Yi-Chen
YC
Institute of Polymer Science and Engineering, National Taiwan University, Taipei, Taiwan.
Hsieh
Wen-Yuan
WY
Young
Tai-Horng
TH
D002021:Buffers; D016923:Cell Death; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D004912:Erythrocytes / Q000166:cytology; D006384:Hemagglutination; D006639:Histidine / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008422:Materials Testing; D008856:Microscopy, Fluorescence; D009841:Oligonucleotides / Q000737:chemistry / Q000378:metabolism*; D010316:Particle Size; D011073:Polyamines / Q000737:chemistry / Q000378:metabolism*; D000071228:Polyelectrolytes; D011108:Polymers / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D014162:Transfection / Q000379:methods*
D002021:Buffers; D004247:DNA; D006639:Histidine; D009841:Oligonucleotides; D011073:Polyamines; D000071228:Polyelectrolytes; D011108:Polymers; C063994:polyallylamine