Abstract
Intelligent stimulus-triggered release and high drug-loading capacity are crucial requirements for drug delivery systems in cancer treatment. Based on the excessive intracellular GSH expression and pH conditions in tumor cells, a novel glutathione (GSH) and pH dual-responsive hydrogel was designed and synthesized by conjugates of glutamic acid-cysteine dendrimer with alginate (Glu-Cys-SA) through click reaction, and then cross-linked with polyethylene glycol (PEG) through hydrogen bonds to form a 3D-net structure. The hydrogel, self-assembled by the inner disulfide bonds of the dendrimer, is designed to respond to the GSH heterogeneity in tumors, with a remarkably high drug loading capacity. The Dox-loaded Glu-Cys-SA hydrogel showed controlled drug release behavior, significantly with a release rate of over 76% in response to GSH. The cytotoxicity investigation indicated that the prepared DOX-loaded hydrogel exhibited comparable anti-tumor activity against HepG-2 cells with positive control. These biocompatible hydrogels are expected to be well-designed GSH and pH dual-sensitive conjugates or polymers for efficient anticancer drug delivery.
Highlights
IntroductionWide ranges of anticancer drugs receive accelerated approval every year
Academic Editor: Satomi OnoueCurrently, wide ranges of anticancer drugs receive accelerated approval every year.the adverse side effects due to the poverty of pharmacological targets remain serious problems that are difficult to overcome [1,2]
The introduction of polyethylene glycol (PEG) significantly increased the strength of hydrogel by forming hydrogen-bond interactions between the thiol groups and the hydroxyl group of PEG
Summary
Wide ranges of anticancer drugs receive accelerated approval every year. The adverse side effects due to the poverty of pharmacological targets remain serious problems that are difficult to overcome [1,2]. The drawbacks include low water solubility, drug stability, and high efflux from cells, which constrain the therapeutic effects of drugs in tumor treatment [3]. How to deliver drugs to the target site (tissues or cells) and release therapeutic concentrations efficiently and safely are the main challenges for innovations to chemotherapeutic agents. The discovery and design of stimulus-sensitive agents according to the differences of pH and redox potential between normal cells and tumor cells has been extensively explored in recent years [4,5,6,7].
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