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Synthesis and Self-assembly of Amphi...

Gu, Renpeng.

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Synthesis and Self-assembly of Amphiphilic DNA Copolymers.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Synthesis and Self-assembly of Amphiphilic DNA Copolymers./
作者:	Gu, Renpeng.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2018,
面頁冊數:	166 p.
附註:	Source: Dissertations Abstracts International, Volume: 79-11, Section: B.
Contained By:	Dissertations Abstracts International79-11B.
標題:	Pharmaceutical sciences. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10744129
ISBN:	9780355871425

Synthesis and Self-assembly of Amphiphilic DNA Copolymers.
Gu, Renpeng.

Synthesis and Self-assembly of Amphiphilic DNA Copolymers. - Ann Arbor : ProQuest Dissertations & Theses, 2018 - 166 p.

Source: Dissertations Abstracts International, Volume: 79-11, Section: B.

Thesis (Ph.D.)--Duke University, 2018.

This item is not available from ProQuest Dissertations & Theses.

The unique structural and chemical properties of DNA enable it as a polymeric building material in bionanotechnology. Conjugating hydrophobic moieties to DNA chains makes DNA amphiphiles that can self-assemble into various architectures. Because of the great biocompatibility of DNA materials, DNA amphiphiles is of great interest in the field of targeted drug delivery. To build desirable drug delivery vehicles, controlling the size and morphology is critical since these factors influence the circulation time and cellular uptake. There are many studies on controlling the self-assembly behavior of DNA amphiphiles by tuning the hydrophilic-to-hydrophobic balance. However, the synthesis of DNA amphiphiles is usually challenging due to the incompatible solubility between the hydrophilic DNA chains and hydrophobic moieties. In specific aim 1, we explored terminal deoxynucleotidyl transferase catalyzed enzymatic polymerization (TcEP) to synthesize a series of di/triblock DNA amphiphiles. TcEP can easily control the length of synthesized ssDNA (hydrophilic-to-hydrophobic balance) and directly incorporate hydrophobic moieties containing unnatural nucleotides into the growing ssDNA to construct a hydrophobic block. This strategy can avoid the incompatible solubility issue. By tuning the hydrophilic-to-hydrophobic balance, we controlled the DNA assemblies' size and morphology. For example, diblock DNA amphiphiles self-assembled into star-like and crew-cut micelles. Triblock DNA amphiphiles self-assembled into flower-like micelles. The observed self-assembly behaviors also agree with the predictions from dissipative particle dynamics (DPD) simulations. Photo-responsive drug delivery vehicles attract increasing attention as they enable control over drug release spatially and temporally with ease. In specific aim 2, we developed a type of photo-responsive DNA amphiphiles by conjugating DNA with azobenzene using copper-free click reaction. Due to switchable polarities of azobenzene under UV or visible light irradiation, the hydrophilic-to-hydrophobic balance of DNA-azobenzene conjugates is also switchable, resulting in photo-controlled micellar self-assembly and disassembly in aqueous media. Nuclease stability is another critical challenge to applying DNA based materials in vivo, such as drug delivery vehicles. Nucleases in the blood stream may degrade DNA strands, which disintegrates the DNA-based drug delivery vehicles and releases the encapsulated drugs before they reach the targeted region. In specific aim 3, we developed a strategy to enhance the stability of DNA via the incorporation of nucleotides containing unnatural nucleobases using TcEP. These unnatural nucleobases make the DNA a poor substrate for nucleases binding. We discovered that by increasing the size and density of the unnatural nucleobases, the half-life of synthesized DNA is significantly increased in the presence of exo-, endonuclease and human serum. In summary, the research describes in this dissertation aims to develop self-assembled DNA amphiphiles with designed structures, stimulus-responsiveness, and enhanced stability against nuclease degradation to advance their potential in drug delivery application.

ISBN: 9780355871425Subjects--Topical Terms:

3173021
Pharmaceutical sciences.

Synthesis and Self-assembly of Amphiphilic DNA Copolymers.
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