A host/guest assembled hyaluronic acid-based supramolecular hydrogel with NIR-steered degradation capacity for enhanced tumor therapy through programmable drug release.

Recently, a variety of stimulus-responsive hydrogel platforms have been developed, specifically designed to respond to changes in physiological signals within the disease microenvironment. However, due to the restricted regulation of drug release behavior in vivo by such hydrogel systems, the precise control of drug release kinetics has not been achieved. Therefore, developing precise drug delivery platforms that enable programmable and "on-off" delivery remains a challenge in this field. This study involved a supramolecular hydrogel platform (HACF) constructed with β-cyclodextrin-modified hyaluronic acid (HA-CD) and ferropentaene-modified hyaluronic acid (HA-Fc) for precise drug delivery and chemo-photothermal therapy by leveraging host-guest interactions between CD and Fc. The phthalocyanine green (ICG) and doxorubicin (DOX) were incorporated into the hydrogel network as photosensitizer and anticancer model drugs. Results demonstrated that ICG facilitated controlled disintegration of the hydrogel and led to responsive release of DOX in vitro under near-infrared (NIR) light stimulation. Furthermore, in vivo findings confirmed that NIR-steered programmed drug release from the hydrogel effectively enhanced anti-tumor efficacy and prevented tumor recurrence. In conclusion, this innovative NIR-driven supramolecular hydrogel platform not only presented a novel approach for remote and precise drug release but also provides a new platform for locally intelligent treatment across various clinical conditions.