Cancer
immunotherapy has emerged as a promising approach to cancer
treatment in recent years. The physical and chemical properties of
nanocarriers are critical factors that regulate the immune activation
of antigen-presenting cells (APCs) in the tumor microenvironment (TME).
Herein, we extensively investigated the behavior of liposome nanoparticles
(Lipo-NPs) with different elasticities, focusing on their interaction
with immune cells and their transport mechanisms from tumors to tumor-draining
lymph nodes (tdLNs). Successfully preparing Lipo-NPs with distinct
elastic properties, their varied behaviors were observed, concerning
immune cell interaction. Soft Lipo-NPs exhibited an affinity to cell
membranes, while those with medium elasticity facilitated the cargo
delivery to macrophages through membrane fusion. Conversely, hard
Lipo-NPs enter macrophages
via classical cellular uptake pathways. Additionally, it was noted
that softer Lipo-NPs displayed superior transport to tdLNs in vivo,
attributed to their deformable nature with lower elasticity. As a
result, the medium elastic Lipo-NPs with agonists (cGAMP), by activating
the STING pathway and enhancing transport to tdLNs, promoted abundant
infiltration of tumor-infiltrating lymphocytes (TILs), leading to
notable antitumor effects and extended survival in a melanoma mouse
model. Furthermore, this study highlighted the potential synergistic
effect of medium elasticity Lipo-NPs with immune checkpoint blockade
(ICB) therapy in preventing tumor immune evasion. These findings hold
promise for guiding immune-targeted delivery systems in cancer immunotherapy,
particularly in vaccine design for tdLNs targeting and eradicating
metastasis within tdLNs.