Smart drug delivery systems for immunotherapeutic agents: focus on biological/biogenic platform-based intelligent delivery in cancer immunotherapy.

Cancer immunotherapy marks a major advance in oncology, yet its effectiveness is constrained by challenges such as inefficient tumor targeting, immune-related toxicities, low response rates, and an immunosuppressive tumor microenvironment (TME). To overcome these obstacles, smart drug delivery systems (SDDSs) have been developed to deliver immunotherapeutic agents in a targeted, controlled manner in response to specific stimuli. This review summarizes recent advances in SDDSs for cancer immunotherapy, focusing on biological and biogenic platforms. These systems respond to endogenous and exogenous stimuli to improve treatment precision and enhance antitumor immune responses. The main types of SDDS, including synthetic, biological, and hybrid, are reviewed in the context of applications such as immune checkpoint inhibition, cancer vaccines, cytokine therapy, and adoptive cell therapy. The review also considers engineered exosomes, including isolation and engineering strategies, microRNA (miRNA) loading strategies, and surface modifications to improve targeting and impact on the TME. Existing evidence suggests that biological and hybrid platforms offer advantages in biocompatibility, biological recognition, and functional versatility; however, challenges remain in cargo-loading efficiency, biological heterogeneity, scalability, safety, and reproducibility. Emerging approaches, including clustered regularly interspaced short palindromic repeats (CRISPR)-based engineering, hybrid nanocarriers, and artificial intelligence, can accelerate the development of advanced immunotherapy delivery systems. Overall, biointegrated SDDSs show potential for greater precision, efficacy, and safety in cancer immunotherapy, although significant barriers to their clinical application remain.