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Design, synthesis, and characterizat...

Joralemon, Maisie Jane.

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Design, synthesis, and characterization of surface-decorated shell crosslinked nanoparticles as tunable biologically-active agents.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Design, synthesis, and characterization of surface-decorated shell crosslinked nanoparticles as tunable biologically-active agents./
作者:	Joralemon, Maisie Jane.
面頁冊數:	215 p.
附註:	Source: Dissertation Abstracts International, Volume: 66-10, Section: B, page: 5429.
Contained By:	Dissertation Abstracts International66-10B.
標題:	Chemistry, Polymer. -
ISBN:	9780542344930

Design, synthesis, and characterization of surface-decorated shell crosslinked nanoparticles as tunable biologically-active agents.
Joralemon, Maisie Jane.

Design, synthesis, and characterization of surface-decorated shell crosslinked nanoparticles as tunable biologically-active agents. - 215 p.

Source: Dissertation Abstracts International, Volume: 66-10, Section: B, page: 5429.

Thesis (Ph.D.)--Washington University, 2005.

Shell crosslinked nanoparticles (SCKs) are multi-functional scaffolds, from which biologically-active ligands can be presented and within which therapeutics can be sequestered and released, that are good candidates as drug delivery vehicles. In this dissertation research, fundamental studies were performed to develop synthetic methodologies for functionalization of SCKs with ligands and to demonstrate their surface accessibility and bioavailability. Two different synthetic methodologies were developed and two different types of biologically-active ligands were incorporated.

ISBN: 9780542344930Subjects--Topical Terms:

1018428
Chemistry, Polymer.

Design, synthesis, and characterization of surface-decorated shell crosslinked nanoparticles as tunable biologically-active agents.
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245 1 0 $a Design, synthesis, and characterization of surface-decorated shell crosslinked nanoparticles as tunable biologically-active agents.
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500 $a Source: Dissertation Abstracts International, Volume: 66-10, Section: B, page: 5429.
500 $a Chair: Karen L. Wooley.
502 $a Thesis (Ph.D.)--Washington University, 2005.
520 $a Shell crosslinked nanoparticles (SCKs) are multi-functional scaffolds, from which biologically-active ligands can be presented and within which therapeutics can be sequestered and released, that are good candidates as drug delivery vehicles. In this dissertation research, fundamental studies were performed to develop synthetic methodologies for functionalization of SCKs with ligands and to demonstrate their surface accessibility and bioavailability. Two different synthetic methodologies were developed and two different types of biologically-active ligands were incorporated.
520 $a In the first synthetic approach, the SCKs were functionalized by assembling mixed micelles from chain-end functionalized and non-functionalized amphiphilic diblock copolymers and then crosslinking the corona. The biologically active ligands were placed at the hydrophilic chain terminus of the amphiphilic block copolymers through the sequential atom transfer polymerization (ATRP) of tert-butyl acrylate and methyl acrylate from mannosylated or 2,4-dinitrophenylated alkyl bromide initiators. The poly(tert-butyl acrylate) blocks were rendered hydrophilic upon removal of the tert-butyl groups to yield poly(acrylic acid) blocks. Non-functionalized amphiphilic diblock copolymers were synthesized in a similar fashion from ethyl 2-bromopropionate to yield polymers of similar compositions as the chain-end functionalized polymers. Incorporation of the mannosylated or 2,4-dinitrophenylated block copolymers into micellar assemblies followed by shell crosslinking then afforded robust SCKs capable of targeting the mannose receptors on bacterial cells or DNP-specific antibodies respectively.
520 $a In the second synthetic approach, Click chemistry, based on the Huisgen 1,3-dipolar cycloaddition between azides and alkynes, was employed to produce SCKs by crosslinking the shell with a multifunctional dendritic crosslinker, and also to perform subsequent chemical modifications and labeling of the SCKs. The dendritic crosslinkers, bearing Click-reactive groups were synthesized, divergently, with triazole linkages between each generation as a result of the Click reaction. The dendrimer core, 1st, 2nd, and 3rd generation dendrimers were tested as crosslinkers for a micelle corona that had been partially functionalized with alkynyl groups. Only the 1st generation dendrimer proved a successful shell crosslinker of micelles in aqueous solution, to yield shell Click crosslinked nanoparticles (SCCKs). Remaining azide termini of the dendrimer crosslinker were utilized to covalently attach acetylene-functionalized fluorescein via Click chemistry.
590 $a School code: 0252.
650 4 $a Chemistry, Polymer. $3 1018428
650 4 $a Chemistry, Organic. $3 516206
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790 1 0 $a Wooley, Karen L., $e advisor
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