Pressure-induced amorphous zeolitic imidazole frameworks with reduced toxicity and increased tumor accumulation improves therapeutic efficacy In vivo.
Pressure-induced amorphous zeolitic imidazole frameworks with reduced toxicity and increased tumor accumulation improves therapeutic efficacy In vivo.
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压力诱导的无定形沸石咪唑骨架具有降低的毒性和增加的肿瘤积累，提高了体内治疗效果
DOI：
10.1016/j.bioactmat.2020.08.036
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发表时间：
2021-03
影响因子：
18.9
通讯作者：
Wu A
中科院分区：
文献类型：
--
作者：
Jiang Z;Li Y;Wei Z;Yuan B;Wang Y;Akakuru OU;Li Y;Li J;Wu A
沸石咪唑骨架材料（ZIFs）因其载药量高、孔径合适、具有pH响应性药物释放等特点，在纳米医学中得到了广泛应用。然而，在循环过程中药物快速释放、对小鼠主要器官产生意外毒性、在肺部出现不良的长期累积甚至导致死亡等问题，目前阻碍了它们在体内生物医学方面的应用。在此，我们报道了一种通过压力诱导非晶化制备的高载5 - 氟尿嘧啶（5 - Fu）的非晶态ZIF - 8（aZIF - 8）。与ZIF - 8相比，这种纳米系统避免了在循环过程中药物的早期释放，并提供了肿瘤微环境响应性的药物释放，在体外细胞活力和体内评估的存活率方面都有所提高。此外，在相同的注射剂量下，aZIF - 8比ZIF - 8具有更长的血液循环时间和更低的肺部累积。aZIF - 8/5 - Fu在循环过程中药物释放更少、血液循环时间更长以及生物相容性更好，这显著提高了它在ECA - 109荷瘤小鼠中的治疗效果，并使治疗后50天的存活率达到100%。因此，具有良好生物相容性和长血液循环时间的aZIF - 8有望成为一种在体内有效治疗癌症的有前景的纳米系统。
高压被用于构建非晶态ZIF - 8。
非晶态ZIF - 8减少了血液循环过程中的药物释放，并提高了体外和体内的生物相容性。
在体内，具有更高肿瘤累积量的非晶态ZIF - 8/5 - Fu比ZIF - 8/5 - Fu显示出更好的治疗效果。
Zeolitic Imidazole Frameworks (ZIFs) are widely applied in nanomedicine for their high drug loading, suitable pore size, pH-responsive drug release, and so on. However, fast drug release during circulation, unexpected toxicity to mice major organs, undesirable long-term accumulation in the lung and even death currently hinder their in vivo biomedical applications. Herein, we report an amorphous ZIF-8 (aZIF-8) with high loading of 5-Fu through pressure-induced amorphization. This nano-system avoids early drug release during circulation and provides tumor microenvironment-responsive drug release with improved in vitro cell viability, and survival rate in in vivo evaluations as compared to ZIF-8. Furthermore, aZIF-8 shows longer blood circulation and lower lung accumulation than ZIF-8 at same injected doses. Less drug release during circulation, longer blood circulation, and better biocompatibility of aZIF-8/5-Fu significantly improves its therapeutic efficacy in ECA-109 tumor-bearing mouse, and result in 100% survival rate over 50 days after treatment. Therefore, aZIF-8 with favorable biocompatibility and long blood circulation is expected to be a promising nano-system for efficacious cancer therapy in vivo. High pressure was introduced the construct amorphous ZIF-8. Amorphous ZIF-8 decreased the drug release during blood circulation, and improved the biocompatibility in vitro and in vivo. Amorphous ZIF-8/5-Fu with higher tumor accumulation showed better therapeutic efficacy than ZIF-8/5-Fu in vivo.
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