title: Intracellular accumulation and immunological properties of fluorescent gold nanoclusters in human dendritic cells.
abstract: We have studied the effect of highly fluorescent gold nanoclusters (Au NCs) (∅ < 3 nm) stabilized by different ligands on the intracellular accumulation and immune response of human derived-monocyte dendritic cells (DCs). Results indicate that the high uptake efficiency of Au NCs is strongly related to their small size and to the nature of the ligand, with zwitterionic ligands being more effective than PEGylated ones. Evidence from flow cytometry and microscopy demonstrate time and concentration-dependent Au NCs internalization by endocytic pathway(s) involving amorphous and laminar organelles, while maintaining their discrete size and photoluminescence properties. The uptake of zwitterionic ligand-stabilized Au NCs induced very low cytotoxicity and a strong immunosuppressive response (Th1/Treg pattern), associated with a DC maturation state. This behavior contrasts to the effect of bigger particles (∼12 nm size) which induced a cytotoxic response involving Natural Killer (CD56) cells. Overall, this study stresses the critical importance of particle size and ligand type on the immunostimulation of DCs and highlights the remarkable potential of this new class of nanomaterial as a novel vaccine platform.
authors.affiliation: Research Laboratory and Allergy Service, IBIMA, Regional University Málaga Hospital, UMA, Málaga, Spain.
authors.forename: Tahia D
authors.initials: TD
authors.lastname: Fernández
authors.affiliation: The Andalusian Centre for Nanomedicine and Biotechnology (BIONAND) Nano-imaging Unit (Junta de Andalucía-Universidad de Malaga), Málaga, Spain.
authors.forename: John R
authors.initials: JR
authors.lastname: Pearson
authors.affiliation: Diagnostic Area, The Andalusian Centre for Nanomedicine and Biotechnology, BIONAND (Junta de Andalucia-Universidad de Malaga), Málaga, Spain.
authors.forename: Manuel Pernia
authors.initials: MP
authors.lastname: Leal
authors.affiliation: Research Laboratory and Allergy Service, IBIMA, Regional University Málaga Hospital, UMA, Málaga, Spain; Allergy Service, Carlos Haya Hospital, Málaga, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Torres
authors.affiliation: Research Laboratory and Allergy Service, IBIMA, Regional University Málaga Hospital, UMA, Málaga, Spain; Allergy Service, Carlos Haya Hospital, Málaga, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Blanca
authors.affiliation: Research Laboratory and Allergy Service, IBIMA, Regional University Málaga Hospital, UMA, Málaga, Spain; Allergy Service, Carlos Haya Hospital, Málaga, Spain.
authors.forename: Cristobalina
authors.initials: C
authors.lastname: Mayorga
authors.affiliation: Therapeutic Nanosystems, The Andalusian Centre for Nanomedicine and Biotechnology, BIONAND, Málaga, Spain. Electronic address: xleguevel@bionand.es.
authors.forename: Xavier
authors.initials: X
authors.lastname: Le Guével
mesh_terms: D000588:Amines / Q000737:chemistry; D019002:CD56 Antigen / Q000378:metabolism; D049109:Cell Proliferation; D003713:Dendritic Cells / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D005434:Flow Cytometry; D005456:Fluorescent Dyes / Q000737:chemistry*; D006046:Gold / Q000737:chemistry*; D006801:Humans; D007107:Immune System; D007166:Immunosuppressive Agents / Q000737:chemistry; D008024:Ligands; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry*; D018613:Microscopy, Confocal; D050997:Nanomedicine; D010316:Particle Size
chemical_list: D000588:Amines; D019002:CD56 Antigen; D005456:Fluorescent Dyes; D007166:Immunosuppressive Agents; D008024:Ligands; D006046:Gold
keywords: Cellular uptake; Fluorescence; Gold nanoclusters; Immune response; Monocyte-derived dendritic cells