Direct Transfer of Mesoporous Silica Nanoparticles between Macrophages and Cancer Cells

SIMPLE SUMMARY: A challenge for Nanomedicine is delivery to the site of action, most commonly the tumor microenvironment. When injected systemically, scavenger cells, such as macrophages, rapidly sequester nanoparticles. This study asks if macrophages can directly deliver scavenged nanoparticles to cancer cells via cellular connections known as tunneling nanotubes. Knowledge of the in vivo cellular fate of nanoparticles is critical for the design of optimized nanocarriers for clinical translation. ABSTRACT: Macrophages line the walls of microvasculature, extending processes into the blood flow to capture foreign invaders, including nano-scale materials. Using mesoporous silica nanoparticles (MSNs) as a model nano-scale system, we show the interplay between macrophages and MSNs from initial uptake to intercellular trafficking to neighboring cells along microtubules. The nature of cytoplasmic bridges between cells and their role in the cell-to-cell transfer of nano-scale materials is examined, as is the ability of macrophages to function as carriers of nanomaterials to cancer cells. Both direct administration of nanoparticles and adoptive transfer of nanoparticle-loaded splenocytes in mice resulted in abundant localization of nanomaterials within macrophages 24 h post-injection, predominately in the liver. While heterotypic, trans-species nanomaterial transfer from murine macrophages to human HeLa cervical cancer cells or A549 lung cancer cells was robust, transfer to syngeneic 4T1 breast cancer cells was not detected in vitro or in vivo. Cellular connections and nanomaterial transfer in vivo were rich among immune cells, facilitating coordinated immune responses.