Abstract
AbstractIn this work, we developed novel stimuli-responsive injectable hydrogels composed of a highly biocompatible cartilage acellularized matrix (CAM) and a water-soluble cross-linker containing a diselenide bridge by using ultrafast norbornene (Nb)-tetrazine (Tz) click chemistry. The cross-linking reaction between the Nb groups of the CAM and Tz groups of the cross-linker evolved nitrogen gas and resulted in injectable hydrogels with highly porous structures. The synthesized hydrogels demonstrated high drug loading efficiencies (up to 93%), good swelling ratios, and useful mechanical properties. The doxorubicin (DOX)-loaded hydrogels released minimal amounts of DOX in the simulated physiological medium; however, sustained release of DOX was detected under reducing conditions, revealing more than 90% DOX release after 96 h. Interestingly, the indocyanine green (ICG)-incorporated hydrogels produced reactive oxygen species upon exposure to NIR light and exhibited burst release (>50% DOX release) of DOX during the first 4 h, followed by a sustained release phase. In vitro cytocompatibility tests showed that the synthesized CAM-Nb and hydrogels are essentially nontoxic to HFF-1 fibroblast cells and human colorectal adenocarcinoma cells (HT-29), indicating their excellent bioorthogonality and biocompatibility. Furthermore, DOX-loaded and DOX + ICG-loaded hydrogels inhibited the metabolic activities of HT-29 cells after GSH or NIR exposure and induced antitumor effects similar to those of free DOX. Therefore, these biocompatible and reduction-responsive injectable hydrogels, which exhibited on-demand drug release after NIR exposure, could be promising candidates for minimally invasive local delivery of cancer therapeutics.
Funder
National Research Foundation of Korea
Publisher
Springer Science and Business Media LLC
Subject
Condensed Matter Physics,General Materials Science,Modeling and Simulation,Condensed Matter Physics,General Materials Science,Modeling and Simulation
Cited by
25 articles.
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