期刊
ACS APPLIED MATERIALS & INTERFACES
卷 10, 期 3, 页码 2328-2337出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsami.7b16522
关键词
drug delivery; autophagy; ZIF-8; 3-methyladenine; antitumor; metal-organic frameworks
资金
- National Natural Science Foundation of China [21473157, 21503190]
- Science Technology Department of Zhejiang Province [2015C03034]
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.
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