Derivative of Epigallocatechin-3-gallatea Encapsulated in ZIF-8 with Polyethylene Glycol–Folic Acid Modification for Target and pH-Responsive Drug Release in Anticancer Research

Abstract

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.

Synthesis and modification of ZIF-8 and its application in drug delivery and tumor therapy

“…37610 | RSC Adv., 2020, 10, 37600-37620 74 Hyaluronic acid (HA) is a hydrophilic natural polysaccharide with negative charge, which is abundant in the extracellular matrix and possesses good biocompatibility, non-toxicity, and biodegradability. In addition, HA can actively target certain tumor cells and bind to the over-expressed CD44 receptor on the surface of tumor cells.…”

In situ triggering antitumor efficacy of alcohol-abuse drug disulfiram through Cu-based metal-organic framework nanoparticles

“…These drug-loaded MOF are usually synthesized by the "one-pot method”, which is simple and time-saving 6 . More importantly, they can maintain stable under neutral conditions, but disintegrate in the acidic tumor microenvironment, leading to selectively drug release at target site 10 , 22 , 23 , 24 , 25 . Consequently, it is desirable to take advantages of Cu-based MOF to encapsulate DSF for cancer chemotherapy, which can deliver both Cu 2+ and DSF into tumor, and thus trigger in situ toxicity against tumor cells.…”

“…Furthermore, the systemic half-life time, chemical stability, safety consideration and targeting biodistribution of MOF system should be also considered 24 . As a natural polysaccharide, hyaluronic acid (HA) has been widely used for modifying nanocarriers to improve the water solubility, biocompatibility, and tumor targetability 26 , 27 , 28 .…”

Evaluation of the Biological Activity of Folic Acid-Modified Paclitaxel-Loaded Gold Nanoparticles

“…Besides, it can improve the water solubility of a poorly soluble drug, improving its reach to tumor cells and efficacy. [37][38][39][40][41][42] In this study, a drug-loading system Au@MPA-PEG-FA-PTX was prepared and evaluated using MTT assay for targeting efficiency. FA modified AuNPs showed improved targeting in a series of cell experiments that estimated apoptosis, mitochondrial membrane potential (MMP), and the levels of intracellular ROS.…”

“…Besides, it can improve the water solubility of a poorly soluble drug, improving its reach to tumor cells and efficacy. 37–42 …”