Rod Scale Design Strategies for Immune-Targeted Delivery System towards Cancer Immunotherapy.

Strengthening the antitumor immune response to surpass the activation energy barrier associated with the immunosuppressive tumor microenvironment is an active area of cancer immunotherapy. Emerging evidence suggests that delivery of immunostimulatory molecules with the aid of carrier system is essential for cancer immunotherapy. However, the size-dependent effect of delivery system on immune-targeted sites and anti-cancer immune responses is yet to be comprehensively understood. Herein, to clarify the size-dependent effect of delivery system on underlying anti-cancer immune mechanism, rod-shaped hydroxyapatite (HA) particles with length from 100 nm to 10 μm are designed. HA rods stimulate anti-cancer immunity in a size-dependent manner. Shorter HA rods with length ranging from 100 to 500 nm promote antigen cellular uptake, dendritic cells (DCs) maturation and lymph nodes targeting of antigen. In contrast, longer HA rods with length ranging from 500 nm to 10 μm prolong antigen retention and increase DCs accumulation. Medium-sized HA rods with length of 500 nm, taking the advantages of both short and long rods, show optimized antigen release and uptake, increased DCs accumulation and maturation, highest CD4+ and CD8+ T cells population and the best anti-cancer immunity in vivo. The present study provides a rod scale design strategy for immune-targeted delivery system towards cancer immunotherapy in the future.