DNA nanostructure-based systems for drug and nucleic acid delivery
DNA 나노구조 기반 약물 전달 연구
- 약학대학 약학과
- Issue Date
- 서울대학교 대학원
- DNA nanostructures; rolling circle amplification; drug delivery; aptamer; graphene oxide; reduced graphene oxide
- 학위논문 (박사)-- 서울대학교 대학원 : 약학과 약제과학전공, 2015. 8. 오유경.
- Rolling circle amplification (RCA)-based DNA nanotechnologies have attracted tremendous interest to develop new platform of drug delivery. First, DNA nanoballs with antisense oligonucleotide (ASO)-complementary sequences could provide sequence-specific loading of dual ASOs, Dz13 and OGX-427, and coating with hyaluronic acid (HA) promoted CD44 receptor-mediated delivery of ASOs to tumor cells. Importantly, ASOs delivered by HA-coated DNA nanoballs silenced the expression of their target mRNAs of ASO, exerting potent anticancer effects in vitro and in vivo. Second, DNA polyaptamer nanothreads of protein tyrosine kinase 7 (PTK7) receptor were synthesized by RCA. To enhance the anchoring capability of polyaptamers onto reduced graphene oxide (rGO), oligonucleotide bridge sequence between repeating aptamer sequences was introduced. Surface modification of rGO with DNA polyaptamer nanothreads (PNTrGO) resulted in improved cellular uptake into PTK7-positive tumor cell lines and enhanced tumor tissue accumulation compared to oligoT-bridged scrambled polyaptamer-anchored rGO nanosheets. Moreover, systemic administration of doxorubicin using PNTrGO enhanced the antitumor effects in mice bearing PTK7-positive tumors. Third, an injectable hydrogel based on drug-specific DNA polyaptamer networks was developed by using graphene oxide (GO) nanosheets as a crosslinker. Graphene oxide-crosslinked DNA polyaptamer (GO-PA) hybrid hydrogels were constructed by running single step RCA of DNA template in the presence of GO nanosheet. GO-PA hybrid hydrogel showed drug-specificity towards kanamycin. The drug loading efficiency of GO-PA was 58.0 % for kanamycin, but 1.2% for gentamicin.