title: Surface functionalization of polymeric nanospheres modulates macrophage activation: relevance in leishmaniasis therapy.
abstract: OBJECTIVE
  To characterize the production and application of carbohydrate functionalized poly(D,L-lactide-co-glycolide) (PLGA) nanospheres as immune-modulatory mediators in the treatment of visceral leishmaniasis (VL).
  
  
  METHODS
  PLGA nanospheres were prepared by nanoprecipitation and surface functionalized with mannose, mannan or mannosamine moieties using a carbodiimide reaction. Flow cytometry and fluorescence microscopy revealed the interaction of these nanospheres with macrophages.
  
  
  RESULTS
  The nanocarriers were taken up by murine primary macrophages using clathrin-mediated endocytosis. Co-culture of macrophages with carbohydrate-functionalized nanospheres led to their activation and production of pro-inflammatory cytokines. One dose of amphotericin B-loaded on mannan-functionalized nanospheres resulted in an efficacy VL therapy.
  
  
  CONCLUSIONS
  This approach provides a promising therapy for VL and a new therapeutic nanoplatform for obligate intracellular pathogens.
authors.affiliation: IBMC-INEB, Infection & Immunology Unit - Parasite Disease Group, University of Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal.
authors.forename: Daniela
authors.initials: D
authors.lastname: Barros
authors.forename: Sofia A
authors.initials: SA
authors.lastname: Costa Lima
authors.forename: Anabela
authors.initials: A
authors.lastname: Cordeiro-da-Silva
mesh_terms: D000666:Amphotericin B / Q000008:administration & dosage*; D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry*; D019344:Lactic Acid / Q000737:chemistry* / Q000276:immunology; D007896:Leishmaniasis / Q000188:drug therapy / Q000276:immunology; D008262:Macrophage Activation / Q000187:drug effects*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D008351:Mannans / Q000737:chemistry / Q000276:immunology; D008358:Mannose / Q000737:chemistry / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D054118:Nanospheres / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*
chemical_list: D000981:Antiprotozoal Agents; D016207:Cytokines; D004337:Drug Carriers; D008351:Mannans; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D000666:Amphotericin B; D008358:Mannose
keywords: PLGA nanospheres; carbohydrates; immunotherapy; mannose receptors; murine primary macrophages