Logo image
利用形態學改變之多功能複合型奈米微胞於癌症標的、顯影及治療之應用
Thesis

利用形態學改變之多功能複合型奈米微胞於癌症標的、顯影及治療之應用

張哲豪
Masters, National Tsing Hua University
2008

Abstract

正六角形微胞光敏感劑形態學 hexagonal micellephotodynamic therapymorphology
AbstractThis study concentrates on the morphology of drug carrier and how it would effect on different endocytosis of cells. In many researches, there have demonstrated shape of drug carrier with direct relationship to avoid capture by immune system and increase efficiency of drug delivery. We invented unique self-assembly hexagonal mixed micelles by using pH sensitive diblock copolymer encapsulate photodynamic drug A (5,10,15,20-Tetrekis(pentafluorophenyl)-21H,23H-porphine). Photosensitive agent with symmetric formula tended to form crystallized aggregate. Generally, hydrophobic photosensitive agent would precipitate when it under poor solvent. By that time hydrophobic-hydrophilic diblocok copolymer encapsulated the drug A, the drug will encapsulated by polymer with hexagonal nano scale form. In contrast, drug B (5,10,15,20-Tetrakis(4-hydroxyphenyl)-21H,23H-porphine) loading mixed micelles were observed form as spherical particles. For bio-imaging of drug carrier, we also synthesized diblock copolymer that included Cy5.5 fluorescent dye. The characteristics and morphologies of mixed micelles were analyzed from 1H-NMR, DLS, zeta potential, AFM, and TEM.In vitro experiment data observed hexagonal mixed micelles owned selectivity between mouse alveolar macrophage cell (MHS) and HeLa cell by confocal microscopy. They couldn’t be swallowed easily by macrophage, even if changed external surface components. Then if the drug carriers’ shape changed to spherical mixed micelles, they could be observed great amounts accumulation in macrophages and HeLa cells. The cytotoxicity of drug loading mixed micelles with hexagonal drug carriers against HeLa cell was much greater than MHS cell, but spherical drug carriers were the same. Mixed micelles accumulation and bio-distribution observed by in vivo optical imaging (Near IR) at various time. Hexagonal mixed micelles also showed more efficiency on accumulating than spherical mixed micelles on cancer cells from biodistribution analysis of mice. This study presents a new nano-scale hexagonal structure for drug carrier development. Moreover, hexagonal micelles show more efficiency than traditional spherical micelles on cancer targeting.

Metrics

1 Record Views

Details

Logo image