title: 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 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.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Mi-Gyeong
authors.initials: MG
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Joo Yeon
authors.initials: JY
authors.lastname: Park
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Gayong
authors.initials: G
authors.lastname: Shim
authors.affiliation: College of Pharmacy, Hanyang University, Ansan, Republic of Korea.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 151-742, Republic of Korea. Electronic address: ohyk@snu.ac.kr.
authors.forename: Yu-Kyoung
authors.initials: YK
authors.lastname: Oh
mesh_terms: D040761:Biomimetic Materials / Q000008:administration & dosage / Q000138:chemical synthesis; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D016373:DNA, Antisense / Q000008:administration & dosage* / Q000235:genetics*; D004058:Diffusion; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D054118:Nanospheres / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009374:Neoplasms, Experimental / Q000235:genetics* / Q000628:therapy*; D010316:Particle Size; D014162:Transfection / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D016373:DNA, Antisense; D053769:Nanocapsules
keywords: Antisense oligonucleotides; Biomimetic condensation; DNA nanoballs; Rolling circle amplification; Sequence-specific loading