Intracellular carriers based on poly (amino acid)-derivatives and their application as anticancer drug and sphingolipid carriers = 폴리아미노산 유도체를 이용한 세포 내 전달체의 합성과 이의 항암제 및 스핑고지질 전달체로써의 응용에 관한 연구

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Phytosphingosine grafted poly (L-amino acid)-derivatives were synthesized and their various self-assembled structures were studied as carriers for anticancer drugs and phytosphingosine itself. By controlling the grafting ratio of phytosphingosine to poly (L-amino acid)-derivative backbone polymers, self-assembled structures of diverse morphology were prepared and their unique self-assembling behavior was studied. The objective of this thesis was to design the adequate self-assembled structures to efficiently deliver anticancer drugs and phytosphingosine and to enhance anticancer therapeutic actions of phytosphingosine. In chapter 2, a series of poly (2-hydroxyethyl L-aspartamide)-g-phytosphingosine, PHEA-$\it{g}$-PHS with different degree of substitution (DS) of PHS, was prepared and their self-assembling behavior was investigated. Spherical micelle-like aggregates was identified for physical delivery of phytosphingosine with optimized physicochemical properties including a uniform and nanoscopic size, low critical aggregation concentration, enhanced kinetic stability, and high loading capacity of drug, which were characterized with DLS, TEM, and fluorescence spectroscopy. For application as intracellular drug carriers, the uptake mechanism of polymeric micelle-like aggregates and phytosphingosine loaded ones were studied with confocal laser scanning microscopy and flow cytometery. Polymeric micelle-like aggregates from PHEA-$\it{g}$-PHS was effectively localized in the entire cytososol even though they do not have any ligands specifically to interact with the cells on their surface. The uptake studies at endocytosis inhibition conditions suggested that the internalization of the aggregates was temperature and energy-dependent process and the colocalization of endosomes-specific marker confirmed the mechanism of uptake is to be endocytosis. The uptake of the aggregates was increased with incubation time and concentration of polymers. The trafficking studie...
Kim, Jong-Dukresearcher김종득researcher
한국과학기술원 : 생명화학공학과,
Issue Date
455376/325007  / 020065880

학위논문(박사) - 한국과학기술원 : 생명화학공학과, 2010.08, [ xi, 103 p. ]


sphingolipid-metabolite; poly(amino acid)-derivative; self-assembly; amphiphilic graft copolymer; phytosphingosine; 파이토스핑고신; 스핑고지질대사물; 폴리아미노산유도체; 자기회합; 양친성그라프트고분자

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