Delivery of rapamycin-loaded nanoparticle down regulates ICAM-1 expression and maintains an immunosuppressive profile in human CD34+ progenitor-derived dendritic cells.
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.
Das
Saswati
S
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8. saswati@ualberta.ca
Haddadi
Azita
A
Veniamin
Simona
S
Samuel
John
J
D018952:Antigens, CD34 / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006801:Humans; D007165:Immunosuppression Therapy; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D022423:Myeloid Cells / Q000166:cytology / Q000187:drug effects; D053758:Nanoparticles / Q000008:administration & dosage* / Q000648:ultrastructure; D010641:Phenotype; D011100:Polyglycolic Acid / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D020123:Sirolimus / Q000008:administration & dosage* / Q000494:pharmacology*; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D013499:Surface Properties; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000235:genetics / Q000378:metabolism
D018952:Antigens, CD34; D016207:Cytokines; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D018799:Intercellular Adhesion Molecule-1; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020123:Sirolimus