透過您的圖書館登入
IP:18.221.11.62
  • 學位論文

開發玫瑰紅裝載之複合高分子材料作為光激發藥物控制釋放之奈米平台

Development of rose bengal-loaded multipolymeric nanoplateform as photo-responsive drug carrier for cancer therapy

指導教授 : 黃郁棻

摘要


玫瑰紅(Rose Bengal)具有優良的光敏化效率,能產生大量的單態氧,於光動力治療領域深具應用潛力。過去研究可透過直接修飾如醋酸化、或藉由奈米載體攜帶,協助藥物抵達並累積於腫瘤微環境,並提升其穿越細胞膜之能力,達到有效傳遞藥物之目的。本研究主要利用甲殼素(chitosan)、聚乙烯醇(Polyvinyl alcohol)、混合短鏈聚乙烯亞胺(Polyethylenimine),以油水乳化法將疏水性氧化鐵奈米粒子包覆於奈米團簇中,作為光動力藥物載體。此複合體除具有良好的水溶分散性,聚乙烯亞胺之陽離子聚電解質特性,亦可藉由靜電吸引力,減少負電性玫瑰紅分子於中性環境下之滲漏問題;一旦施予光照,玫瑰紅的光敏化作用會產生大量活性氧分子,進而氧化聚乙烯亞胺之三級胺集團,造成奈米團簇之表面電位下降,使玫瑰紅分子從載體中釋放,達到光動力控制藥物釋放之目的。磁性鐵奈米粒子能在本體系中進一步扮演磁共振造影對比劑的顯影功能,以及提供磁力導引靶向式藥物傳遞,利用磁性導引以及光動力誘導藥物釋放可以達到高準確性的藥物傳遞及癌症治療。 綜合上述,本研究提出簡單而快速的合成方法,不須額外的化學性修飾以及共聚合高分子的製程,利用單純的高分子及藥物摻雜,並以靜電作用力以及親疏水作用力進行合成,完成一對氧化壓力敏感之新穎複合高分子材料,利用聚乙烯亞胺之陽離子特性,在光敏化反應中的可調控性,可控制負電性藥物或核糖核酸的吸附與釋放,開發出有別於傳統光動力治療,一智慧型之癌症治療奈米平台。

並列摘要


Rose bengal (RB) which exhibits high singlet oxygen (1O2) yield is a clinical promising photosensitizer in anticancer therapy. Several RB hydrophobic derivatives (e.g., acetate) have been developed to facilitate intracellular accumulation. Nanoparticles also serve as effective carriers to deliver these compounds to the tumor microenvironment, or to cross biological barriers such as cell membranes. In this study, RB molecules were encapsulated in a mixture of chitosan, polyvinyl alcohol and branched polyethylenimine (bPEI) with hydrophobic iron oxide nanoparticles through an oil-in-water emulsion method. The as-prepared multipolymeric magnetic nanoclusters displayed high water dispersibility and the cationic groups of bPEI were effective for RB loading through electrostatic interaction. In addition, triggered release of the loaded drugs also occurred simultaneously during the photodynamic reaction. The improvement of photodynamic-stimulated triggered release holds great promise in precise control of drug delivery.

並列關鍵字

無資料

參考文獻


1. Love, J.C., et al., Self-Assembled Monolayers of Thiolates on Metals as a Form of Nanotechnology. Chemical Reviews, 2005. 105(4): p. 1103-1170.
2. Daniel, M.-C. and D. Astruc, Gold Nanoparticles:  Assembly, Supramolecular Chemistry, Quantum-Size-Related Properties, and Applications toward Biology, Catalysis, and Nanotechnology. Chemical Reviews, 2003. 104(1): p. 293-346.
3. Sapsford, K.E., et al., Functionalizing Nanoparticles with Biological Molecules: Developing Chemistries that Facilitate Nanotechnology. Chemical Reviews, 2013. 113(3): p. 1904-2074.
4. Eustis, S. and M.A. El-Sayed, Why gold nanoparticles are more precious than pretty gold: Noble metal surface plasmon resonance and its enhancement of the radiative and nonradiative properties of nanocrystals of different shapes. Chemical Society Reviews, 2006. 35(3): p. 209-217.
5. de Lima, R., A.B. Seabra, and N. Durán, Silver nanoparticles: a brief review of cytotoxicity and genotoxicity of chemically and biogenically synthesized nanoparticles. Journal of Applied Toxicology, 2012. 32(11): p. 867-879.

延伸閱讀