Smart Approach for InSitu One-Step Encapsulation and Controlled Delivery of a Chemotherapeutic Drug using Metal-Organic Framework-Drug Composites in Aqueous Media
Smart Approach for InSitu One-Step Encapsulation and Controlled Delivery of a Chemotherapeutic Drug using Metal-Organic Framework-Drug Composites in Aqueous Media
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DOI：
10.1002/cphc.201501012
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发表时间：
2016-04-04
期刊：
影响因子：
2.9
通讯作者：
Chakraborty, Anjan
中科院分区：
文献类型：
--
作者：
Adhikari, Chandan;Chakraborty, Anjan
研究了抗癌药物阿霉素(DOX)在不同外界刺激下从金属有机骨架(MOF)药物复合材料中的控释行为。以1，3，5-苯三甲酸(H3BTC)为有机配体，以醋酸铁和硝酸锌为金属源合成了生物相容性较好的Fe-BTC和Zn-BTC金属有机化合物。与传统方法相比，原位形成的MOF-药物复合材料具有更高的载药量。目前的方法没有任何额外的步骤来加载合成后的药物。此外，药物的载药量也与MOF的孔大小无关，因为药物分子在原位形成时嵌入到MOF中。药物释放在外界刺激下进行监测，包括改变酸性pH和生物相容脂质体存在超过72小时。稳态荧光光谱用于监测药物释放随时间的变化，激光共聚焦扫描显微镜用于揭示阿霉素在脂质体存在下的释放后的去向。结果表明，Zn-BTC-DOx复合制剂的释药速率高于Fe-BTC-DOx复合制剂。这归因于DOX与Fe-BTC的结合强于DOX与锌-BTC的结合。这项研究为在水介质中制备MOF-药物复合材料提供了一种新的方法，用于未来的生物医学应用。
Controlled release of an anticancer drug, doxorubicin (dox), from metal-organic framework (MOF)-drug composites is demonstrated under different external stimuli. 1,3,5-Benzenetricarboxylic acid (H3BTC) is used as an organic ligand, and iron acetate and zinc nitrate are used as metal sources to synthesize Fe-BTC and Zn-BTC MOFs, which are known to be biocompatible. The insitu formation of MOF-drug composites demonstrates high drug loading capacity compared to conventional methods. The present methodology is devoid of any extra steps for loading the drug after synthesis. Moreover, the drug loading is also independent of pore size of the MOF as the drug molecules are embedded inside the MOF during their insitu formation. The drug release was monitored under external stimuli including change to acidic pH and the presence of biocompatible liposomes for a period of more than 72h. Steady-state fluorescence spectroscopy is used to monitor the drug release as a function of time and confocal laser scanning microscopy is used to unravel the post-release fate of doxorubicin in the presence of liposomes. It is found that drug release rate is higher for the Zn-BTC-dox composite than for the Fe-BTC-dox composite. This is attributed to the stronger binding between dox and Fe-BTC than that between dox and Zn-BTC. This study highlights a novel approach for the preparation of MOF-drug composites in an aqueous medium for future biomedical applications.