title: 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.
authors: Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8. saswati@ualberta.ca
authors: Saswati
authors: S
authors: Das
authors: Azita
authors: A
authors: Haddadi
authors: Simona
authors: S
authors: Veniamin
authors: John
authors: J
authors: Samuel
mesh_terms: 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
chemical_list: 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