Biomimetic DNA nanoballs for oligonucleotide delivery

Abstract Here, we designed biomimetic DNA nanoballs for delivery of multiple antisense oligonucleotides (ASOs). DNA templates with ASOs-complementary sequences were amplified by rolling circle amplification (RCA). RCA products were loaded with two types of ASOs by hybridization, condensed using aden...

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Bibliographic Details
Published in:Biomaterials 2015-09, Vol.62, p.155-163
Main Authors: Kim, Mi-Gyeong, Park, Joo Yeon, Shim, Gayong, Choi, Han-Gon, Oh, Yu-Kyoung
Format: Article
Language:English
Subjects:
Advanced Basic Science
Amplification
Antisense oligonucleotides
Biomimetic condensation
Biomimetic Materials - administration & dosage
Biomimetic Materials - chemical synthesis
Cell Line, Tumor
Cell Survival - drug effects
Cell Survival - genetics
Cellular
Dentistry
Deoxyribonucleic acid
Diffusion
DNA nanoballs
DNA, Antisense - administration & dosage
DNA, Antisense - genetics
Genetic Therapy - methods
Humans
Nanocapsules - administration & dosage
Nanocapsules - chemistry
Nanocapsules - ultrastructure
Nanospheres - administration & dosage
Nanospheres - chemistry
Nanospheres - ultrastructure
Nanostructure
Neoplasms, Experimental - genetics
Neoplasms, Experimental - therapy
Oligonucleotides
Particle Size
Peptides
Rolling circle amplification
Sequence-specific loading
Surgical implants
Transfection - methods
Treatment Outcome
Tumors
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Summary:Abstract Here, we designed biomimetic DNA nanoballs for delivery of multiple antisense oligonucleotides (ASOs). DNA templates with ASOs-complementary sequences were amplified by rolling circle amplification (RCA). RCA products were loaded with two types of ASOs by hybridization, condensed using adenovirus-derived Mu peptide, and coated with hyaluronic acid (HA) for delivery into CD44-overexpressing tumor cells. HA-coated, Mu peptide-condensed, dual ASO-loaded DNA nanoballs (HMA nanoballs) showed considerable cellular entry of Cy5-incorporated RCA product DNA and fluorescent ASOs, whereas Mu peptide-condensed, dual ASO-loaded DNA nanoballs (MA nanoballs) revealed limited uptake. Dual ASOs, Dz13 and OGX-427, delivered by HMA nanoballs could reduce the levels of protein targets and exert anticancer effects. Enhanced tumor distribution was observed for fluorescent HMA nanoballs than the corresponding MA nanoballs. Upon intravenous co-administration with doxorubicin, HMA nanoballs exerted the greatest anti-tumor effects among the groups. These results suggest HMA nanoballs as a nanoplatform for sequence-specific delivery of multiple ASOs and other functional oligonucleotides.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2015.04.037