Nanodrug delivery systems in tumor immunotherapy: From immune activation to tumor reprogramming

Nanodrug delivery systems (NDDSs) offer distinctive advantages in tumor immunotherapy, not only by enhancing drug distribution, targeting, and bioavailability but also by actively engaging in immune regulation through multiple mechanisms. In recent years, researchers have increasingly recognized that the NDDS itself can act as a pivotal driver in immune activation, participating in the induction of immunogenic cell death (ICD), the activation of dendritic cells (DCs) and T cells, the reprogramming of immunosuppressive cell populations, and the remodeling of the tumor immune microenvironment (TIME). Various nanomaterial platforms are undergoing a functional transition from "drug carriers" to "immune amplifiers." These systems are capable of spatiotemporally orchestrating synergistic responses between innate and adaptive immunity or directly modulating immune cells through specific signaling pathways to establish durable immune memory. This review systematically summarizes the key design principles and immune-activating mechanisms of diverse nanocarriers, and discusses their prospective applications in immunotherapy, particularly in combination with other therapeutic modalities. Emerging approaches, including AI-driven strategies, as well as current challenges are also highlighted. The work aims to provide theoretical foundations and design insights for the development of intelligent, immune-driven NDDSs that can advance the next generation of precision cancer immunotherapy.