Hydrogel-dependent strategies to modulate the tumor microenvironment for improved anti-tumor treatment.

Abstract

Cancer remains a leading cause of death worldwide, and effective therapies are still urgently needed. Although chemotherapy, surgery, radiotherapy, and immunotherapy have advanced cancer treatment, their efficacy and safety are often limited by the antagonistic tumor microenvironment (TME). Drug delivery systems across nano-, micro-, and macroscale dimensions offer opportunities to remodel the TME by improving pharmacokinetics and coordinating therapeutic modalities. Among them, hydrogels are particularly attractive owing to their tunable microstructures, high loading capacity, and manufacturing scalability. This review summarizes recent advances in drug-loaded hydrogels for TME modulation in tumor immunotherapy, focusing on strategies for remodeling hot and cold tumors, including immune-desert and immune-excluded phenotypes, their underlying immunological mechanisms, and key translational challenges.