Journal
ACS BIOMATERIALS SCIENCE & ENGINEERING
Volume 4, Issue 12, Pages 4183-4192Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsbiomaterials.8b00840
Keywords
EGCG derivative; ZIF-8; pH response; targeting; anticancer
Categories
Funding
- National Natural Science Foundation of China [21473157, 21503190]
- Science Technology Department of Zhejiang Province [2015C03034]
- Pancreas Disease Accurate Diagnosis and Treatment Clinical Medical Innovation Center, Zhejiang University
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Epigallocatechin-3-gallatea (EGCG), a key component of tea, has been found to have anticancer activity but poor stability. To improve its antioxidative stability and widen the application of EGCG in anticancer therapy, a kind of EGCG derivative, EGCG palmitate (PEGCG), was synthesized and encapsulated in ZIF-8 nanoparticles with functionalization of folic acid (FA), which is commonly used as pH-responsive drug carrier. PEGCG encapsulated in polyethylene glycol (PEG)-FA/ZIF-8 nanoparticles (PEG-FA/PEGCG@ZIF-8 NPs) exhibits sixfold improvement of stability compared to that of free PEGCG. With target recognition between folic acid (FA) on the surface of NPs and overexpressed FA receptor (FR) in cancer cells, the NPs can be efficiently internalized into cells and present targeted effects of inhibition growth on HeLa cells (cancer cells) compared with HEK 293 cells (normal cells), consistent with the regulation of reactive oxygen species (ROS) level and the induction of autophagy. The detection of autophagy flux and the measurement of autophagy marked proteins in cells suggest that autophagy flux and the autophagosome formation are appreciably induced when the cells were treated with PEG-FA/PEGCG@ZIF-8 NPs. It indicates that pH-responsive PEG-FA/PEGCG@ZIF-8 NPs with target identification for cancer cells can be used as highly efficient drug carriers in targeting cancer chemotherapy.
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