DC Field | Value | Language |
---|---|---|
dc.contributor.advisor | Kim, Jong-Duk | - |
dc.contributor.advisor | 김종득 | - |
dc.contributor.author | Yang, Seung-Rim | - |
dc.contributor.author | 양승림 | - |
dc.date.accessioned | 2011-12-13T01:39:48Z | - |
dc.date.available | 2011-12-13T01:39:48Z | - |
dc.date.issued | 2005 | - |
dc.identifier.uri | http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=249374&flag=dissertation | - |
dc.identifier.uri | http://hdl.handle.net/10203/28970 | - |
dc.description | 학위논문(박사) - 한국과학기술원 : 생명화학공학과, 2005.8, [ xii, 167 p. ] | - |
dc.description.abstract | Various biocompatible polymeric delivery systems were designed by covalently conjugating specific functionalities to poly(amino acid) derivatives to address intracellular delivery barriers. The physicochemical properties of synthesized polymeric systems in aqueous solution were characterized, and the cellular uptake and therapeutic effect was mainly evaluated. In the first part of this work, oligoarginine ($Arg_8$) as a cell-penetrating peptide was conjugated to poly(2-hydroxytethyl aspartamide) (PHEA) via a thioether linkage to enhance the intracellular delivery of macromolecular delivery systems. The cellular uptake was analyzed by confocal laser scanning microscopy and flow cytometry. $PHEA-Arg_8$ conjugate was effectively localized in both fixed and unfixed HeLa cells. The studies at endocytosis inhibition conditions suggested that the internalization of $PHEA-Arg_8$ into cells was a temperature- and energy-dependent process and the colocalization with an endocytosis marker revealed an endocytosis was a key mechanism in the internalization of $PHEA-Arg_8$. The fluorescence spectra of $PHEA-Arg_8$ in liposome solutions showed $PHEA-Arg_8$ was collectively adsorbed in negative liposome membrane due to the high cationic property of conjugated $Arg_8$, representing a surface adsorption was a first step in the internalization of $PHEA-Arg_8$. The membrane leakage activity of $PHEA-Arg_8$ was much lower than that of $Arg_8$ own, meaning $PHEA-Arg_8$ does not effectively disrupt the cell membrane integrity. The uptake of polymer conjugates was increased with incubation time and reached saturation after several hours. The increase of the number of peptide conjugated to one polymer chain could increase the collective adsorption of polymer conjugates and enhance the cellular uptake by an adsorptive-endocytosis. Oligoarginine $(Arg_8)$ was also successfully conjugated to alkyl chain grafted poly(2-hydroxyethyl aspartamide) $(PHEA-C_{18}-Arg_8)$ via a thioether li... | eng |
dc.language | eng | - |
dc.publisher | 한국과학기술원 | - |
dc.subject | drug delivery | - |
dc.subject | poly(amino acid) | - |
dc.subject | cell-penetrating peptide | - |
dc.subject | polymeric carrier | - |
dc.subject | Intracellular delivery | - |
dc.subject | anticancer drug | - |
dc.subject | 항암제 | - |
dc.subject | 약물전달 | - |
dc.subject | 폴리아미노산 | - |
dc.subject | 세포막 투과성 펩타이드 | - |
dc.subject | 고분자 전달체 | - |
dc.subject | 세포 내 전달 | - |
dc.title | Novel intracellular delivery carriers based on poly(amino acid)s | - |
dc.title.alternative | 폴리아미노산 유도체를 이용한 새로운 세포 내 전달체의 개발 및 응용에 대한 연구 | - |
dc.type | Thesis(Ph.D) | - |
dc.identifier.CNRN | 249374/325007 | - |
dc.description.department | 한국과학기술원 : 생명화학공학과, | - |
dc.identifier.uid | 020025172 | - |
dc.contributor.localauthor | Kim, Jong-Duk | - |
dc.contributor.localauthor | 김종득 | - |
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