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3-Helix Micelles as Nanocarriers -- ...

Ang, JooChuan.

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3-Helix Micelles as Nanocarriers -- Understanding Hierarchical Structures, Kinetic Pathway, and Controlling Multivalency.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	3-Helix Micelles as Nanocarriers -- Understanding Hierarchical Structures, Kinetic Pathway, and Controlling Multivalency./
作者:	Ang, JooChuan.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2016,
面頁冊數:	130 p.
附註:	Source: Dissertation Abstracts International, Volume: 78-10(E), Section: B.
Contained By:	Dissertation Abstracts International78-10B(E).
標題:	Materials science. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10251398
ISBN:	9781369842371

3-Helix Micelles as Nanocarriers -- Understanding Hierarchical Structures, Kinetic Pathway, and Controlling Multivalency.
Ang, JooChuan.

3-Helix Micelles as Nanocarriers -- Understanding Hierarchical Structures, Kinetic Pathway, and Controlling Multivalency. - Ann Arbor : ProQuest Dissertations & Theses, 2016 - 130 p.

Source: Dissertation Abstracts International, Volume: 78-10(E), Section: B.

Thesis (Ph.D.)--University of California, Berkeley, 2016.

This dissertation focuses on fundamental understanding of the hierarchical nanostructure and kinetic pathway of self-assembled sub-20 nm 3-helix micelles. 3-helix micelles are formed by self-assembly of a new family of amphiphilic peptide-PEG-lipid hybrid conjugates. Structural deconvolution of this complex, hierarchically assembled multi-component system is non-trivial and delineating the structural components is crucial to reveal structural insights into the organization of building block constituents. Furthermore, decoupling the effect of each component on the self-assembly kinetic pathway is imperative to appreciate their contribution towards the overall energy landscape of the system for future design of nanocarriers. The knowledge gained from these studies provides insight to identify design parameters that will facilitate the development of nanocarriers based on 3-helix micelles.

ISBN: 9781369842371Subjects--Topical Terms:

543314
Materials science.

3-Helix Micelles as Nanocarriers -- Understanding Hierarchical Structures, Kinetic Pathway, and Controlling Multivalency.
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245 1 0 $a 3-Helix Micelles as Nanocarriers -- Understanding Hierarchical Structures, Kinetic Pathway, and Controlling Multivalency.
260 1 $a Ann Arbor : $b ProQuest Dissertations & Theses, $c 2016
300 $a 130 p.
500 $a Source: Dissertation Abstracts International, Volume: 78-10(E), Section: B.
500 $a Adviser: Ting Xu.
502 $a Thesis (Ph.D.)--University of California, Berkeley, 2016.
520 $a This dissertation focuses on fundamental understanding of the hierarchical nanostructure and kinetic pathway of self-assembled sub-20 nm 3-helix micelles. 3-helix micelles are formed by self-assembly of a new family of amphiphilic peptide-PEG-lipid hybrid conjugates. Structural deconvolution of this complex, hierarchically assembled multi-component system is non-trivial and delineating the structural components is crucial to reveal structural insights into the organization of building block constituents. Furthermore, decoupling the effect of each component on the self-assembly kinetic pathway is imperative to appreciate their contribution towards the overall energy landscape of the system for future design of nanocarriers. The knowledge gained from these studies provides insight to identify design parameters that will facilitate the development of nanocarriers based on 3-helix micelles.
520 $a 3-helix micelles demonstrate immense potential as a nanocarrier for drug delivery to the brain due to its ability to bypass the blood-brain barrier and accumulate within glioblastoma tumors in rat models. To bridge the gap in knowledge between biological performance of 3-helix micelles and fundamental structure-function correlation, the hierarchical structure and assembly kinetic pathway are studied in detail.
520 $a Unraveling the internal structure of 3-helix micelle using contrast variation small-angle neutron scattering revealed a slightly deformed side-conjugated PEG and ~85 v/v% of 3-helix micelle is comprised of water. The entropic deformation of PEG likely contributes to the high kinetic stability of 3-helix micelles whereas the high water content has significant repercussions on the mechanical properties of 3-helix micelles as a nanocarrier and could shed light on the extravasation properties of 3-helix micelles through biological barriers.
520 $a The self-assembly pathway of peptide-PEG-lipid conjugates at the air-water interface to form trimeric coiled-coils was shown to be dependent on the applied lateral pressure. PEGylated amphiphiles based on 3-helix bundle-forming peptides form a mixture of dimers and trimers at intermediate pressure and converts to trimers completely upon high surface pressure. PEG acts to mediate the interaction between bundles and preserves the coiled-coil structural integrity upon high compression.
520 $a The energy landscape of 3-helix micelle formation was also delineated to understand the role of each component within the building block contributes toward the overall self-assembly process. The key factor in determining the kinetic stability is the formation of trimeric coiled-coil bundles in the corona of 3-helix micelles, providing greater energetic barriers for subunits to overcome to dissociate from the micelle. Hydrophobic packing of alkyl chains contributes to a lesser degree to the overall kinetic stability, but plays a key role in the internal structural reorganization during the formation of trimeric coiled-coils.
520 $a The fundamental knowledge gained from structural and kinetic aspects of 3-helix micelle self-assembly process was applied to a mixture of two coiled-coil-based amphiphiles to generate a mixed micelle nanocarrier platform that provides control over the local multivalent state of ligands on the micelle surface. Tracking the distribution of the two amphiphiles within the mixed micelle indicated that they phase separate into regions enriched in one amphiphile. The ability to control multivalent ligand presentation as well as generation of 'patchy' mixed micelles suggests this nanocarrier platform based on 3-helix micelles has potential for ligand-targeted drug delivery applications.
520 $a Lastly, the conjugation architecture of di-alkyl chains attached to the peptide headgroup was studied to probe how alkyl packing can influence micelle stability. The results showed that highly splayed di-alkyl chains can pack more efficiently, leading to enhanced alkyl melting transition temperatures and increased stability without significantly disrupting the peptide secondary and tertiary structure. This demonstrates that conjugation architecture of alkyl chains can be a useful design parameter to manipulate the stability of 3-helix micelles.
590 $a School code: 0028.
650 4 $a Materials science. $3 543314
650 4 $a Nanoscience. $3 587832
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710 2 $a University of California, Berkeley. $b Materials Science & Engineering. $3 1669540
773 0 $t Dissertation Abstracts International $g 78-10B(E).
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