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Self-Assembled Single Stranded DNA-Amphiphiles for Targeted Drug Delivery
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Self-Assembled Single Stranded DNA-Amphiphiles for Targeted Drug Delivery. |
| 개인저자 | Harris, Michael. |
| 단체저자명 | University of Minnesota. Chemical Engineering. |
| 발행사항 | [S.l.]: University of Minnesota., 2018. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2018. |
| 형태사항 | 157 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-04B. Dissertation Abstract International |
| ISBN | 9781085762328 |
| 학위논문주기 | Thesis (Ph.D.)--University of Minnesota, 2018. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Advisor: Kokkoli, Efrosini. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | The use of targeted drug delivery has significantly improved the field of medicine in the last 30 years. At the same time, the field of DNA nanotechnology has allowed for the design nanoparticles with exact nanoscale precision. This thesis combines the two fields by using single-stranded DNA amphiphiles, a novel class of biomaterials, to create new targeted drug delivery vehicles.DNA aptamers are a sub-class of single stranded DNA molecules whose three-dimensional structure allows them to bind to one molecule with high affinity. ssDNA-amphiphile micelles were created from a ssDNA aptamer sequence to create a targeted ssDNA micelle for cancer therapies. These targeted micelles were shown to internalize only to cells expressing the aptamer target and release into the cytosol over 24 h. In vivo studies showed that although tumor accumulation of ssDNA-amphiphile micelles is independent of their targeting capability, internalization of the micelles requires the aptamer sequence.DNA-amphiphiles have also been shown to form nanotubes when in aqueous solution, dependent on the exact DNA sequence and lipid tail structure used. One ssDNA-amphiphile that forms nanotubes was used for delivery to mouse glioblastoma cells. The nanotubes were shown to internalize to the glioblastoma cells, but not to healthy mouse astrocytes. When delivered directly to both hemispheres of the brains of mice with tumors in the right hemisphere, retention was observed only in the tumor hemisphere and not in the healthy hemisphere. This observation was conserved when the nanotubes were delivered systemically.The nanotubes were then used for an initial in vitro chemotherapy experiment. When mixed with the chemotherapeutic doxorubicin, the nanotubes released little chemotherapeutic over the course of two weeks, with no significant change in the nanotube structure over this time. When delivered to mouse glioblastoma cells, the doxorubicin - nanotube mixture showed better cell toxicity compared to free doxorubicin. This is a promising result for chemotherapeutic delivery of the nanotubes. |
| 일반주제명 | Chemical engineering. Nanotechnology. Oncology. |
| 언어 | 영어 |
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