Cellular biodistribution of polymeric nanoparticles in the immune system

The biodistribution of polymeric nanoparticles (NPs) is of crucial importance in the development of nanoparticle-based vaccine delivery or immunotherapy for cancer. The purpose of this study was to investigate the kinetics of cellular biodistribution of polymeric NPs in the immune system. Polystyrene (PS) yellow-green nanoparticles (YG-NPs) 500nm in diameter were intravenously (i.v.) injected into the tail veins of mice, and the kinetics of YG-NP biodistribution was followed by harvesting cells at pre-determined time points from various immune organs, including blood, bone marrow, spleen, and lymph nodes and analyzing them by polychromatic flow cytometry. To observe the location of YG-NPs in the spleen after i.v. administration, spleens of mice were isolated at 6h post-injection (p.i.), cryosectioned, immunostained, and examined by confocal microscopy. Our data show that the major phagocytosing cells included granulocytes (B220¯CD11b(+)Gr-1(high)Ly-6C(low)) in the blood and bone marrow and B cells (CD11b¯B220(+)) in the spleen. The kinetics of the phenotypic analysis suggest the potential trans-differentiation of the B220¯CD11b(+)Gr-1(low)Ly-6C(high) subset into B220¯CD11b(+)Gr-1¯Ly-6C¯ double-negative (DN) cells expressing the F4/80 macrophage phenotype in the blood and CD115 in the bone marrow after treatment with YG-NPs. Based on the microscopic analysis of spleen cryosections, the majority of YG-NPs were located in the marginal zones (MZ) and red pulp of the spleen at 6h post-injection (p.i.), allowing further interaction with MZ macrophages and granulocytes. The data obtained in this study demonstrate the kinetics of biodistribution of polymeric nanoparticles in the blood, bone marrow, and spleen at the cellular level.