Emerging strategies in lymph node-targeted nano-delivery systems for tumor immunotherapy.

The emergence of immunotherapy has led to the clinical approval of several related drugs. However, their efficacy against solid tumors remains limited. As the hub of immune activation, lymph nodes (LNs) play a critical role in tumor immunotherapy by initiating and amplifying immune responses. Nevertheless, the intricate physiological structure and barriers within LNs, combined with the immunosuppressive microenvironment induced by tumor cells, significantly impede the therapeutic efficacy of immunotherapy. Engineered nanoparticles (NPs) have shown great potential in overcoming these challenges by facilitating targeted drug transport to LNs and directly or indirectly activating T cells. This review systematically examines the structural features of LNs, key factors influencing the targeting efficiency of NPs, and current strategies for remodeling the immunosuppressive microenvironment of LNs. Additionally, it discusses future opportunities for optimizing NPs to enhance tumor immunotherapy, addressing challenges in clinical translation and safety evaluation.