Novel Biological Functions of ZIF-NP as a Delivery Vehicle: High Pulmonary Accumulation, Favorable Biocompatibility, and Improved Therapeutic Outcome
Novel Biological Functions of ZIF-NP as a Delivery Vehicle: High Pulmonary Accumulation, Favorable Biocompatibility, and Improved Therapeutic Outcome
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ZIF-NP 作为递送载体的新生物学功能：高肺部蓄积、良好的生物相容性和改善的治疗效果
DOI：
10.1002/adfm.201504998
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发表时间：
2016-04-25
影响因子：
19
通讯作者：
Zhang, Qiang
中科院分区：
文献类型：
--
作者：
Li, Suxin;Wang, Keke;Zhang, Qiang
尽管沸石咪唑骨架（ZIF）因其高负载量和pH敏感降解等独特特性而成为一种先进的小分子递送功能材料，但对其生物学功能的了解却极其缺乏。为了鉴定此类运载工具的资格，我们对带有或不带有货物的 ZIF-8 纳米粒子 (ZIF-NP) 进行了设计并在体外和体内进行了全面研究。有趣的是，ZIF-NPs表现出很强的生物粘附性，但其自身内化有限，这增强了膜介导的ROS，并且不同于无机ZnO诱导线粒体介导的活性氧（ROS）而不损伤生物膜。在肺中发现了意想不到的高浓度，这可能是由于纳米载体的粒径和分布所致；然而，随着时间的推移，药物水平急剧下降，显示出药物的快速降解和消除。在给定剂量下，ZIF-NPs在动物试验中表现出相当的生物安全性，其可接受的系统和血液生物相容性证明了其对肝肾功能、免疫细胞、炎症因子等的影响极小。负载氟尿嘧啶的ZIF-NPs（5F@ZIF-NPs）显着改善了裸鼠模型中肺转移肿瘤的治疗效果。一般来说，ZIF-NPs在生物纳米相互作用、肺部蓄积、生物相容性和抗肿瘤治疗方面表现出独特的生物学功能，这赋予它们作为递送载体的潜力。
Though zeolitic imidazole framework (ZIF) emerges as an advanced functional material for small-molecule delivery due to its unique features such as high loading and pH-sensitive degradation, there are extreme short of knowledge regarding its biological functions. To qualify this category of delivery vehicle, ZIF-8 nanoparticles (ZIF-NPs) with or without cargo are engineered and comprehensively investigated in vitro and in vivo. Interestingly, ZIF-NPs demonstrate strong bioadhesion but with limited internalization themselves, which enhance the membrane-mediated ROS and are different from that of inorganic ZnO inducing mitochondria-mediated reactive oxygen species (ROS) without biomembrane damage. Unexpected high concentration is found in lung, probably due to the particle size and distribution of the nanocarriers; however, the drug levels drop dramatically with time, revealing the fast degradation and elimination. At the given doses, ZIF-NPs exhibit reasonably biosafety in animal tests as evidenced by their acceptable system and blood biocompatibilities, and minimal impacts on the liver and renal functions, immune cells, inflammatory factors, etc. ZIF-NPs with fluorouracil loading (5F@ZIF-NPs) significantly improve the therapeutic outcome of lung metastasis tumor in a nude mice model. Generally, ZIF-NPs demonstrate unique biological functions in terms of bio-nano interaction, pulmonary accumulation, biocompatibility, and antitumor therapy, which endow them potential as the delivery vehicles.