MOF Nanoparticles with Encapsulated Autophagy Inhibitor in Controlled Drug Delivery System for Antitumor
MOF Nanoparticles with Encapsulated Autophagy Inhibitor in Controlled Drug Delivery System for Antitumor
复制标题
MOF 纳米粒子在抗肿瘤受控药物输送系统中封装自噬抑制剂
DOI：
10.1021/acsami.7b16522
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发表时间：
2018-01-24
影响因子：
9.5
通讯作者：
Fang, Wenjun
中科院分区：
文献类型：
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作者：
Chen, Xuerui;Tong, Rongliang;Fang, Wenjun
金属有机骨架材料具有高孔隙率、大比表面积和可调的功能性，是一种有效的药物载体。最有前途的MOFs之一是沸石咪唑骨架（ZIF-8）晶体，由于其高负载能力和pH敏感性降解，它是一种用于小分子递送的先进功能材料。作为一种新型载体，ZIF-8纳米颗粒用于控制自噬抑制剂3-甲基腺嘌呤（3-MA）的释放，并防止其在到达目标之前大量消散。参照TEM观察和ICPMS对锌的定量分析，通过纳米颗粒内化促进了包封在ZIF-8中的3-MA（3-MA@ZIF-8 NP）在HeLa细胞中的细胞摄取。3-MA@ZIF-8 NPs处理的HeLa细胞中自噬相关蛋白和自噬通量显示，自噬体形成被显著阻断，这表明pH敏感性解离增加了3-MA等浓度下的自噬抑制效率。在体内实验中，与游离3-MA相比，3-MA@ZIF-8 NP显示出更高的抗肿瘤功效，并抑制自噬相关标志物Beclin 1和LC 3的表达。因此，ZIF-8是一种有效的抗肿瘤治疗药物载体，特别是在抑制癌细胞自噬方面。
High porosities, large surface areas, and tunable functionalities made metal organic frameworks (MOFs) as effective carriers for drug delivery. One of the most promising MOFs is the zeolitic imidazolate framework (ZIF-8) crystal, an advanced functional material for small molecule delivery, due to its high loading ability and pH-sensitive degradation. As a novel carrier, ZIF-8 nanoparticles were used in this work to control the release of an autophagy inhibitor, 3-methyladenine (3-MA), and prevent it from dissipating in a large quantity before reaching the target. The cellular uptake in HeLa cells of 3-MA encapsulated in ZIF-8 (3-MA@ZIF-8 NPs) is facilitated through the nanoparticle internalization with reference to TEM observations and the quantitative analyses of zinc by ICPMS. The autophagy-related proteins and autophagy flux in HeLa cells treated with 3-MA@ZIF-8 NPs show that the autophagosome formation is significantly blocked, which reveals that the pH-sensitive dissociation increases the efficiency of autophagy inhibition at the equivalent concentration of 3-MA. In vivo experiments, when compared to free 3-MA, 3-MA@ZIF-8 NPs show a higher antitumor efficacy and repress the expression of autophagy-related markers, Beclin 1 and LC3. It follows that ZIF-8 is an efficient drug delivery vehicle in antitumor therapy, especially in inhibiting autophagy of cancer cells.