Different leukocyte subsets are targeted by systemic and locoregional administration despite conserved nanomaterial characteristics optimal for lymph node delivery.

Lymph nodes (LNs) house a large proportion of the body's leukocytes. Accordingly, engineered nanomaterials are increasingly developed to direct therapeutics to LNs to enhance their efficacy. Yet while lymphatic delivery of nanomaterials to LNs upon locoregional injection has been extensively evaluated, nanomaterial delivery to LN-localized leukocytes after intravenous administration has not been systematically explored nor benchmarked.

Drug-eluting immune checkpoint blockade antibody-nanoparticle conjugate enhances locoregional and systemic combination cancer immunotherapy through T lymphocyte targeting.

Multiple small molecule immune modulators have been identified as synergistic with immune checkpoint blockade (ICB) in their effects on T lymphocytes, but are limited in their successful application to combination cancer immunotherapy due to their short in vivo retention and lack of affinity for T cells. We engineered an antibody-nanoparticle conjugate (ANC) platform consisting of 30 nm polymer nanoparticles that, due to their size and formulation, efficiently distribute after administration to lymph nodes, tissues highly enriched in lymphocytes that contribute to tumor control mediated by ICB. Displaying monoclonal antibodies against surface-expressed T cell markers, NP delivery in vivo to circulating and lymph node-resident lymphocytes was substantially enhanced, as was delivery of small molecules formulated into the NP by passive encapsulation.