Journal
MOLECULES
Volume 27, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/molecules27010281
Keywords
dendrimer modified hydrogel; GSH- and pH-responsive; anti-tumor activity
Funding
- National Natural Science Foundation of China [31960547, 21762043]
- Open Project of Key Laboratory of Synthetic and Biological Colloids, Ministry of Education [JDSJ2018-07]
- Natural Science Foundation of Xinjiang Province, China [2019D01B20]
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An intelligent stimulus-triggered release dual-responsive hydrogel was designed and synthesized in this study. It can respond to the heterogeneity of GSH and pH conditions in tumors, with a high drug loading capacity and controlled release behavior. The Dox-loaded hydrogel exhibited comparable anti-tumor activity to the positive control.
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.
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