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Rational Design of Spherical Nucleic Acids as Therapeutic Constructs
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| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Rational Design of Spherical Nucleic Acids as Therapeutic Constructs. |
| 개인저자 | Zhu, Shengshuang. |
| 단체저자명 | Northwestern University. Materials Science and Engineering. |
| 발행사항 | [S.l.]: Northwestern University., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 147 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-03B. Dissertation Abstract International |
| ISBN | 9781088319932 |
| 학위논문주기 | Thesis (Ph.D.)--Northwestern University, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-03, Section: B.
Advisor: Mirkin, Chad. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Nucleic acids not only are the building blocks of life but also a class of attractive macromolecular therapeutics. However, the delivery of therapeutic oligonucleotides into cells has been a major challenge due to their large size and highly negatively charged backbone. Spherical nucleic acids (SNAs) are a class of emerging nano-biomaterials that overcome this challenge and thus are highly useful as nucleic acids-based therapeutics. SNAs consist of a nanoparticle core with a dense shell of highly oriented oligonucleotides covalently or non-covalently conjugated to it. SNAs can freely enter numerous cell lines by engaging with scavenger receptors on their surface. Once inside the cells, they can act as potent agents for gene regulation or immunomodulation. In addition, SNA cores can be comprised of bioorganic materials, such as liposomes or polymeric nanoparticles, that provide interior space for encapsulating drugs, opening the possibility for dual therapeutics. These unusual biochemical properties of SNAs make them lead drug candidates in gene regulation and immunomodulation therapies.This thesis further explores the unique properties of SNAs and introduces a new class of SNAs based on polymeric core materials that significantly expand their scope of function. Chapter 1 reviews the field of nanomedicine, especially in the context of SNA development and biochemical properties. Chapter 2 describes the development of a SNA-based topical formulation capable of attenuating abnormal scars. Specifically, liposomal SNAs and AuSNAs were utilized to silence transforming growth factor 1 (TGF棺1), a gene significantly implicated in abnormal scarring, in vitro and in vivo. Limitations of conventional SNA constructs are also discussed in this chapter. Chapter 3 describes the design and synthesis of new poly-lactic-co-glycolic acid (PLGA)-SNAs that address these limitations. Chapter 4 further builds on this polymeric SNA construct and details how they can be used to improve gene regulation efficiency by co-delivering two therapeutic agents within a single SNA. The properties and functions of the PLGA-SNAs, including their colloidal stability, peptide release kinetics, and protein knockdown efficiencies were investigated as a function of SNA structure. Chapter 5 provides concluding remarks about the future outlook of SNA development, building upon the knowledge described in the previous chapters. |
| 일반주제명 | Biomedical engineering. Chemical engineering. Materials science. |
| 언어 | 영어 |
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