Hydrogel integrating engineered bacteriophages and nanoparticles potentiates antigen cross-presentation in tumor-infiltrating DCs for oncolytic immunotherapy.

Adequate production of tumor-associated antigens and their efficient cross-presentation by tumor-infiltrating dendritic cells (DCs) to prime T cells are critical for successful tumor immunotherapy. Herein, we developed a nanocomposite hydrogel for breast cancer immunotherapy by cross-linking oncolytic bacteriophages (RGD-M13-3C phage) and incorporating vitamin E-loaded nanoparticles with DC-targeting capability (VE@NPT). The RGD-M13-3C phage is capable of targeting and lysing tumor cells to release tumor-associated antigens. Meanwhile, VE@NPT targets DCs and releases vitamin E, which reduces oxidized lipid levels and their accumulation in DCs. Consequently, the nanocomposite hydrogel can not only generate abundant tumor-associated antigens but also promote lipid metabolism in DCs, thereby enhancing antigen cross-presentation by DCs. In vitro and in vivo experiments confirmed that the hydrogel suppressed tumor growth and triggered an effective antitumor immune response. This study provides methodologies for enhancing antigen cross-presentation by DCs and improving oncolytic immunotherapy using phage-based composite hydrogels.