Dual-Responsive Alginate Hydrogel Constructed by Sulfhdryl Dendrimer as an Intelligent System for Drug Delivery

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 1; p. 281
• Main Authors: Li, Li, Lei, Dongyu, Zhang, Jiaojiao, Xu, Lu, Li, Jiashan, Jin, Lu, Pan, Le
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 03.01.2022; MDPI
• Subjects: Acids; Alginates; Alginates - chemistry; Alginates - pharmacokinetics; Alginates - pharmacology; Alginic acid; Animals; anti-tumor activity; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - pharmacology; Biocompatibility; Biopolymers; Chemical bonds; Chromatography; Conjugates; Cytotoxicity; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacokinetics; Delayed-Action Preparations - pharmacology; dendrimer modified hydrogel; Dendrimers - chemistry; Dendrimers - pharmacokinetics; Dendrimers - pharmacology; Design; Disulfide bonds; Doxycycline - chemistry; Doxycycline - pharmacokinetics; Doxycycline - pharmacology; Drug delivery; Drug delivery systems; Glutamic acid; GSH- and pH-responsive; Hep G2 Cells; Heterogeneity; Humans; Hydrogels; Hydrogels - chemical synthesis; Hydrogels - chemistry; Hydrogels - pharmacokinetics; Hydrogels - pharmacology; Hydrogen bonding; Hydrogen bonds; Investigations; Mice; Morphology; Neoplasms - drug therapy; Neoplasms - metabolism; Polyethylene glycol; Polymers; Self-assembly; Sodium; Tumor cells; Tumors; China; dendrimer modified hydrogel; GSH- and pH-responsive; anti-tumor activity
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27010281

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 ( ) 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 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.