title: Polyaptamer DNA nanothread-anchored, reduced graphene oxide nanosheets for targeted delivery.
abstract: Here, we report reduced graphene oxide (rGO) nanosheets anchoring receptor-specific polyaptamer nanothreads for targeted drug delivery. DNA polyaptamer nanothreads of protein tyrosine kinase 7 receptor (PTK7) were synthesized by rolling cycle amplification. To strengthen the anchoring of polyaptamer nanothreads onto rGO, oligoT bridge domain was introduced between each repeating PTK7 aptamer sequence. As compared to PTK7 polyaptamer nanothreads alone, PTK7 polyaptamer nanothreads with 22-mer oligoT bridges (PNT) showed higher anchoring capacity onto rGO nanosheets. Nanothread-coated surface morphology of PNTrGO was observed. Coating of PNT did not affect the sizes of rGO, but reduced the zeta potential. In PTK7-negative Ramos cells, the uptake of PNT-anchored rGO (PNTrGO) did not differ from that of oligoT-bridged scrambled polyaptamer-anchored rGO (SNTrGO). However, in CCRF-CEM leukemia cells overexpressing PTK7, the uptake of PNTrGO was 2.1-fold higher than that of SNTrGO after 15 min pulse. In vivo distribution to CCRF-CEM tumor tissues was 2.8-fold higher in PNTrGO than in SNTrGO at 48 h post-injection. In CCRF-CEM xenografted mice, intravenously administered doxorubicin (Dox)-loaded PNTrGO showed the higher antitumor activity than other groups, reducing the tumor weight down to 12% of tumor weights of untreated mice. These results suggest the potential of PNTrGO for target-specific drug delivery nanoplatform.
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: Wenjun
authors.initials: W
authors.lastname: Miao
authors.affiliation: Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science, Seoul National University, Seoul 151-742, Republic of Korea.
authors.forename: Jaiwoo
authors.initials: J
authors.lastname: Lee
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: D000818:Animals; D052157:Aptamers, Nucleotide / Q000008:administration & dosage* / Q000737:chemistry*; D001704:Biopolymers / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D004337:Drug Carriers; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D051379:Mice; D049329:Nanostructures; D010087:Oxides / Q000737:chemistry
chemical_list: D052157:Aptamers, Nucleotide; D001704:Biopolymers; D004337:Drug Carriers; D010087:Oxides; D006108:Graphite
keywords: Drug delivery; Polyaptamer nanothreads; Reduced graphene oxide; Rolling circle amplification