Delivery of rapamycin-loaded nanoparticle down regulates ICAM-1 expression and maintains an immunosuppressive profile in human CD34+ progenitor-derived dendritic cells.

ABSTRACT

Immune responses of dendritic cells (DCs) can be modulated by delivery of adjuvants to alter their maturation profile. The purpose of this study was to generate DCs from CD34(+) cells of human cord blood and characterize the effects of poly(D,L-lactic-co-glycolic acid) (PLGA)-nanoparticle encapsulated rapamycin in generating an immunosuppressive DC. Expression of ICAM-1 (intercellular adhesion molecule), a key molecule in DC-T cell interaction was increased in mature DCs in response to lipopolysaccharide (LPS). When rapamycin was encapsulated in the nanoparticle to maintain DCs in the immature state, ICAM-1 expression was down regulated. When delivered in the free form, rapamycin did not alter the expression of ICAM-1. Cytokine arrays exhibited an immunosuppressive profile of various cytokines in response to the nanoparticulate delivery of rapamycin. In addition, RT-PCR data demonstrated the presence of toll like receptor (TLR) 9 transcripts, although our DCs are myeloid in nature. In summary, our study demonstrates that DCs may be rendered immunosuppressive upon delivery of rapamycin-containing nanoparticles.