An Enzyme-Responsive Nanogel Carrier Based on PAMAM Dendrimers for Drug Delivery

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• 作者：Yao Wang ; Yiyang Luo ; Qiang Zhao ; Zhijian Wang ; Zejun Xu ; Xinru Jia
• 刊名：ACS Applied Materials & Interfaces
• 出版年：2016
• 出版时间：August 10, 2016
• 年：2016
• 卷：8
• 期：31
• 页码：19899-19906
• 全文大小：530K
• 年卷期：0
• ISSN：1944-8252

文摘

G4 PAMAM dendrimer molecules were modified via covalently conjugating RGDC, RAADyC, and PEG chains on the periphery (Mac-1), by which a nanogel drug carrier with enzyme-sensitivity (NG-1) was constructed through an oxidation reaction by using NaIO<sub>4sub> to initiate the chemical cross-link of the functional groups on the periphery of dendrimers. Mac-1 and NG-1 both had a spherelike shape with a relatively uniform size of 20 nm for Mac-1 and 50 nm for NG-1 as evidenced by TEM, SEM, and DLS measurements. NG-1 showed much higher drug loading capacity as compared with that of Mac-1 although the cavities in the dendritic structure were used to encapsulate drug molecules as reported in many literatures. In addition, the size of NG-1 with embedded doxorubicin hydrochloride (DOX) decreased significantly to 15 nm in the presence of elastase, which indicated the decomposition of the nanogel triggered by enzyme, leading to drug release in a sustained manner in vitro. The NG-1 carrier was noncytotoxic and biocompatible, and it achieved the same cytotoxicity as free DOX when the drug molecules were loaded inside. From confocal images, the penetrative process of DOX from nanogel could be clearly observed in 8 h. Such a dendrimer-based nanogel may be a potential nanocarrier for drug delivery in cancer therapy.