Laboratory of Controllable Preparation and Application of Nanomaterials, Key Laboratory of Cryogenics, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, No.29 East Road Zhongguancun, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.
Department of Radiology, First Hospital of China Medical University, Shenyang 110001, People's Republic of China; Key Laboratory of Diagnostic Imaging and Interventional Radiology in Liaoning Province, Shenyang 110001, People's Republic of China.
Biomaterials. 2018 Apr;162:132-143. doi: 10.1016/j.biomaterials.2018.02.022. Epub 2018 Feb 9.
Zeolitic imidazolate frameworks (ZIFs) have attracted great interest as pH-sensitive drug carrier because of high drug loading and intrinsic biodegradability. In this work, a biocompatible NIR and pH-responsive drug delivery nanoplatform based on ZIFs (PDA-PCM@ZIF-8/DOX) is synthesized for in vivo cancer therapy. The biocompatibility of ZIFs is greatly improved by polydopamine (PDA) modifying and proved by cytotoxicity and in vivo acute toxicity evaluation. The degradability is also regulated in an appropriate rate. Due to mild reaction condition of ZIFs, the synthesis and drug loading is achieved in one pot with high loading (37.86%) and encapsulation rate (78.76%). Meanwhile, PDA acts as a photothermal transfer agent to trigger thermal response switch of phase change materials for NIR controlled drug release. Under the dual stimulus of NIR and acid environment, the drug release is as high as 78%, while only 21% is released without stimulus, showing a remarkable effect of control release. In vivo anti-tumor experiments demonstrate the high tumor inhibition rate of photothermal-chemotherapy group with a significant synergistic effect. The biocompatible and biodegradable drug delivery platform based on ZIFs has shown great promise for future clinic cancer therapy.
沸石咪唑酯骨架（ZIFs）作为 pH 敏感型药物载体因其高载药量和固有可生物降解性而受到极大关注。在这项工作中，合成了一种基于 ZIFs 的生物相容性近红外和 pH 响应性药物递送纳米平台（PDA-PCM@ZIF-8/DOX），用于体内癌症治疗。通过聚多巴胺（PDA）修饰极大地提高了 ZIFs 的生物相容性，并通过细胞毒性和体内急性毒性评价进行了验证。降解性也以适当的速率进行调节。由于 ZIFs 的反应条件温和，因此可以在一锅反应中同时进行合成和药物负载，具有高负载量（37.86%）和包封率（78.76%）。同时，PDA 作为光热传递剂，触发相变材料的热响应开关，实现近红外控制药物释放。在近红外和酸性环境的双重刺激下，药物释放率高达 78%，而没有刺激时仅释放 21%，显示出显著的控制释放效果。体内抗肿瘤实验表明，光热化疗组具有很高的肿瘤抑制率，具有显著的协同作用。基于 ZIFs 的生物相容性和可生物降解性药物递送平台为未来的临床癌症治疗展示了广阔的前景。
