Lipid-based delivery systems for dendritic cell targeting: Formulation strategies and cancer applications

Cancer immunotherapy has transformed the treatment landscape across multiple tumor types, yet sustained clinical responses remain limited to a subset of patients. As the professional antigen-presenting cells, dendritic cells (DCs) play a central role in initiating and shaping anti-tumor immunity by presenting tumor-associated antigens to naïve T cells and priming specific T cell-mediated responses. Accordingly, strategies that harness or enhance DC function offer promising avenues to improve immunotherapeutic efficacy. Recent advances in the nanomedicine field have led to the development of diverse lipid-based delivery systems (LBDS) tailored to target DCs. These systems enable the (co-)delivery of tumor antigens, adjuvants, and immunomodulatory molecules to promote DC activation, migration, and effective T-cell priming. In this review, we provide a comprehensive overview of LBDS strategies for DC-targeting, including active targeting, through receptor-specific ligands, and passive targeting, that optimize nanoparticle physicochemical properties to enhance uptake. We further evaluate the therapeutic potential of these platforms in preclinical and clinical contexts, highlight the biological and technical challenges in achieving selective delivery to specific DC subsets; and discuss future opportunities to refine these systems. By bridging immunology, nanotechnology, and translational research, this review could guide the development of more potent DC-targeted therapies and accelerate progress toward more effective and durable cancer immunotherapies.