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We have designed and synthesized linear polymerbased nanoconjugates and nanocomplexes bearing multivalent immunostimulatory ligands and also demonstrated that the synthetic multivalent nanocomplexes led to an enhanced stimulation of immune cells in vitro and antitumor and systemic immune memory response in vivo. We have developed hyaluronic acid (HA)-based multivalent nanoconjugates and nanocomplexes for enhanced immunostimulation through the combination of multivalent immune adjuvants with CpG ODNs (as a TLR9 ligand) and cationic poly(l-lysine) (PLL; for the enhancement of cellular uptake). The multivalent HACpG nanoconjugate efficiently stimulated the antigen-presenting cells and the multivalent PLL/HA-CpG nanocomplex also led to an enhanced cellular uptake as well as continuous stimulation of endosomal TLR9. The mice vaccinated with dendritic cells treated with the multivalent nanocomplex exhibited tumor growth inhibition as well as a strong antitumor memory response. [ABSTRACT FROM AUTHOR]

Effective tracking of immunotherapeutic cells is essential for monitoring the migration of injected cells to the target tissue. Here we report the use of near-infrared (NIR) -emitting fluorescent semiconductor nanocrystals, called quantum dots (QDs), for noninvasive in vivo tracking of dendritic cell (DC) migration into lymph nodes. The effect of QDs on DC viability and maturation was systematically investigated using MTT assays and FACS analysis. We found that the labeling of DCs with QDs had no effect on DC phenotype or maturation potential. Cytokine and migration assays revealed that there were no significant changes in either cytokine production or chemokine-dependent migration of QD-labeled DCs relative to unlabeled cells; in both labeled and unlabeled cells, cytokine production and migratory capacity was increased by stimulation with lipopolysaccharide. Furthermore, QDs did not influence allogenic naive T cell activation or uptake of exogenous antigens. Notably, we also demonstrated that it was possible to track QD-labeled DCs injected into the footpad into popliteal and inguinal lymph nodes using NIR fluorescence. Taken together, our protocols establish the potential of noninvasive in vivo imaging of NIR-emitting QDs for tracking immunotherapeutic cells. [ABSTRACT FROM AUTHOR]