Photodegradable Self-Assembling PAMAM Dendrons for Gene Delivery Involving Dendriplexes Formation and Phototriggered DNA Release

碩士 === 中山醫學大學 === 應用化學系碩士班 === 103 === For effective gene delivery, structural degradation of synthetic carriers is crucial to nucleic acids releasing on the transfection time scale. In this study, we have synthesized the amphiphilic dendritic scaffolds with a photolabile o-nitrobenzyl (o-NB) group...

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Bibliographic Details
Main Authors: Yu-Sen Lai, 賴鈺森
Other Authors: 朱智謙
Format: Others
Language:zh-TW
Published: 2015
Online Access:http://ndltd.ncl.edu.tw/handle/85702357366837051341
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Summary:碩士 === 中山醫學大學 === 應用化學系碩士班 === 103 === For effective gene delivery, structural degradation of synthetic carriers is crucial to nucleic acids releasing on the transfection time scale. In this study, we have synthesized the amphiphilic dendritic scaffolds with a photolabile o-nitrobenzyl (o-NB) group that can enable the structural decomposition and controlled release of nucleic acids under active light stimulation. The amphiphilic counterpart composed of a lipophilic cholesterol and hydrophilic poly(amido amine) (PAMAM) dendron allows the self-assembly into a core-shell-like pseudodendrimer above the critical aggregation concentration (CAC) of approximately 20 μM. On the basis of electrostatic interaction, the polycationic pseudodendrimers is capable of forming stable complexes with polyanionic cyclic reporter gene (pEGFP-C1) under low charge excess value, suggesting substantial binding affinity of the dednron assembly toward plasmid DNA. Because the o-NB group in the dendritic structure undergoes efficient photolytic cleavage, in vitro test shows that thus-formed “dendriplexes” are readily dissociated under 365-nm light irradiation, causing effective dendron degradation accompanied by DNA release. This photochemical strategy provides an opportunity to control over the gene binding and releasing in a spatiotemporal manner.