Development of multifunctional polymeric nanoparticles for cancer therapy and imaging applications암 치료와 영상화를 위한 다기능성 고분자 나노입자의 개발

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Pluronic/PEG shell cross-linked nanocapsules encapsulating an oil phase in their nanoreservoir structure was developed as a target-specific carrier for a water insoluble drug, paclitaxel. Oil-encapsulating Pluronic/PEG composite nanocapsules were synthesized by dissolving an oil (Lipiodol) and an amine reactive Pluronic derivative in dichloromethane, and subsequently dispersing in an aqueous solution containing amine-functionalized 6-arm branched poly(ethylene glycol) by ultrasonication. The resultant shell cross-linked nanocapsules had a unique core/shell architecture with an average size of 110.7 ± 9.9 nm at $37^\circ C$, as determined by dynamic light scattering and transmission electron microscopy. Paclitaxel could be effectively solubilized in the inner Lipiodol phase surrounded by a cross-linked Pluronic/PEG shell layer. The paclitaxel-loaded nanocapsules were further conjugated with folic acid to achieve folate receptor targeted delivery. Confocal microscopy and flow cytometric analysis revealed that folate-mediated targeting significantly enhanced the cellular uptake and apoptotic effect against folate receptor over-expressing cancer cells. The present study suggested that these novel nanomaterials encapsulating an oil reservoir could be potentially applied for cancer cell targeted delivery of various water insoluble therapeutic and diagnostic agents. Reducible heparin nanogels cross-linked with disulfide linkages were developed for efficient cellular uptake of therapeutic heparin to induce apoptotic cell death. The heparin nanogels were synthesized by forming nanocomplexes between thiolated heparin and poly(ethylene glycol) in a selected organic solvent, and subsequently producing intermolecular disulfide bonds between thiolated heparin molecules by ultrasonication. The resultant heparin nanogels had a stable structure with an average diameter of 248.7 ± 26.8 nm in aqueous solution. However, they rapidly disintegrated and released free heparin molecule...
Advisors
Park, Tae-Gwanresearcher박태관researcher
Description
한국과학기술원 : 생명과학과,
Publisher
한국과학기술원
Issue Date
2011
Identifier
466365/325007  / 020057253
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생명과학과, 2011.2, [ ix, 82 p. ]

Keywords

Cancer Therapy; Nanoparticles; Polymer; Multifunctional; Biomedical Imaging; 의료 영상; 암 치료; 나노입자; 고분자; 다기능성

URI
http://hdl.handle.net/10203/27719
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=466365&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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