Nanoparticles engineering strategies for lymph-node targeted cancer immunotherapy

• Nanoparticles with <45 nm can rapidly drain into lymph nodes without any carrier. • Negatively charge nanoparticles drain slowly to lymph nodes as compared to positively charge particles from site of injection. • Hydrophobic nanoparticles induce strong antigen specific immune response as compared to hydrophilic nanoparticles. • Active targeting of nanoparticles with surface modification can improve the lymph node homing if nanoparticle size is higher. Recent advancements in understanding the immune system's role in cancer have shifted focus towards immunomodulatory drugs targeting specific immune cells. Lymph nodes (LNs), as key sites for immune response initiation, present a promising target for cancer immunotherapy. This review explores the use of nanotechnology to achieve lymph node-targeted delivery of immunotherapeutics. Various biomaterial-based delivery systems, including polymeric nanoparticles, inorganic nanoparticles, lipid-based, peptide/RNA-based, and virus-based systems have discussed to enhance the effectiveness and safety profile of cancer immunotherapy. The review also delves into the lymphatic architecture, barriers for nanoparticle delivery, and strategies for targeting lymph nodes to improve antigen cross-presentation and adaptive immune responses. A step-by-step approach for nanoparticle-mediated cancer immunotherapy. It begins with the synthesis of nanoparticles that are later delivered to lymph nodes, where they interact with lymphocytes and dendritic cells. The dendritic cells engulf the nanoparticles and present their antigens via MHC-I molecules, which activates cytotoxic T lymphocytes. Finally, these activated T cells infiltrate the tumor microenvironment to target and destroy cancer cells.