Dynamic Diselenide\nHydrogels for Controlled Tumor\nOrganoid Culture and Dendritic Cell Vaccination

Dynamic hydrogels are emerging as advanced materials\nfor engineering\ntissue-like environments that mimic cellular microenvironments. We\nintroduce a diselenide-cross-linked hydrogel system with light-responsive\nproperties, designed for precise control of tumor organoid growth\nand light-initiated radical inactivation, particularly for dendritic\ncell (DC) vaccines. Diselenide exchange enables stress relaxation\nand hydrogel remodeling, while recombination and quenching of seleno\nradicals (Se<sup>•</sup>) reduce cross-linking density, leading\nto controlled degradation. We demonstrate a 2D to 3D growth strategy,\nwhere tumor cells inoculate on the hydrogel surface, expand, and gradually\nform spherical organoids within the 3D hydrogel. These tumor organoids\nshow significantly higher drug resistance compared to 2D-cultured\ncells. High-density light irradiation enhances diselenide exchange,\ninducing hydrogel degradation, tumor cell death, and release of functional\nantigens. This system serves as a dynamic platform for tumor organoid\nculture and antigen release, offering significantly advanced approaches\nfor in vitro tumor modeling and immunological research. Our findings\nposition diselenide-cross-linked hydrogels as versatile materials\nfor precision cellular engineering, with broad applications in cancer\nresearch and beyond.