State Key Laboratory of Rare Earth Resource Utilization, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130022, P. R. China.
Division of Chemistry and Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University, Singapore 637371.
Nanoscale. 2020 Feb 14;12(6):3846-3854. doi: 10.1039/c9nr09869k. Epub 2020 Jan 29.
High treatment efficiency and low drug toxicity are two key factors in tumor therapy. The development of multifunctional drug carrier systems is of great significance for the diagnosis and therapy of tumors. Herein, a novel biodegradable treatment system based on zeolitic imidazolate framework-90 (ZIF-90) was designed in this study. This 5-FU@ZIF-90@ZnO (FZZ) drug delivery system achieves synergistic treatment with antineoplastic 5-fluorouracil (5-FU) and zinc oxide, and also has good dispersibility in the acidic tumor microenvironment (TME), which enables the drug to achieve pH-controlled delivery in acidic organisms. Interestingly, zinc oxide nanoparticles can play a dual role here. They can prevent the premature leakage of drugs under physiological conditions. Moreover, Zn produced after the decomposition of nanoparticles can act as a therapeutic agent, overcoming the tumor resistance to 5-FU and regulating a series of physiological reactions to inhibit tumor growth. It is worth noting that the porous ZIF-90 is an emerging drug carrier with a relatively high drug loading rate of 39% in this study. Synergistic 5-FU and ZnO nanoparticles have achieved tumor inhibition and have shown high therapeutic biosafety. Thus, the FZZ core-shell nanoparticles are a potential pH-controlled drug release system that can be applied to tumor treatment.
高治疗效率和低药物毒性是肿瘤治疗的两个关键因素。多功能药物载体系统的发展对于肿瘤的诊断和治疗具有重要意义。在此，本研究设计了一种基于沸石咪唑酯骨架-90（ZIF-90）的新型可生物降解治疗系统。该 5-氟尿嘧啶（5-FU）@ZIF-90@氧化锌（FZZ）药物递送系统实现了抗肿瘤药物 5-氟尿嘧啶（5-FU）和氧化锌的协同治疗，并且在酸性肿瘤微环境（TME）中具有良好的分散性，使药物能够在酸性生物体中实现 pH 控制释放。有趣的是，氧化锌纳米粒子在此处可以发挥双重作用。它们可以防止在生理条件下药物的过早泄漏。此外，纳米粒子分解后产生的 Zn 可以作为治疗剂，克服肿瘤对 5-FU 的耐药性并调节一系列生理反应以抑制肿瘤生长。值得注意的是，多孔 ZIF-90 是一种新兴的药物载体，在本研究中具有相对较高的 39%的药物载药量。协同的 5-FU 和 ZnO 纳米粒子实现了肿瘤抑制，并表现出了高治疗生物安全性。因此，FZZ 核壳纳米粒子是一种潜在的 pH 控制药物释放系统，可应用于肿瘤治疗。
