An Injectable, Near-Infrared Light-Responsive Click Cross-Linked Azobenzene Hydrogel for Breast Cancer Chemotherapy

Injectable hydrogels possess huge potential as localized drug carriers in breast cancer chemotherapy, owing to several advantages, including easy target administration, enhanced therapeutic efficiency, and less systemic side effects. Herein, we describe an injectable, near-infrared (NIR) light-responsive click cross-linked azobenzene hydrogel (AzoGel) that displays NIR irradiation-mediated smart drug release. The hydrogel can be formed in situ via click cross-linking by mixing two kinds of gelatin derivatives functioned with dibenzylcyclooctyne (DBCO) and azidated azobenzene (N₃-Azo) respectively. The polyacrylic acid (PAA)-coated upconversion nanoparticles (UCNP@PAA)-encapsulated AzoGel has NIR light-responsive characteristics owing to the photoisomerization of azobenzene in the networks. The amount of an anticancer drug doxorubicin (DOX), released from the hydrogel can be efficiently controlled by tuning the exposure time and intensity of 980 nm NIR light. Results of the in vivo study using DOX and UCNP@PAA-loaded AzoGel controlled by NIR light in the 4T1 breast cancer xenograft mouse model demonstrated an enhanced anti-cancer effect. To conclude, the injectable, NIR light-responsive, click cross-linked AzoGel exhibits a high potential as a localized drug delivery platform for cancer therapy.