title: Human immune cell targeting of protein nanoparticles--caveospheres.
abstract: Nanotechnology has the power to transform vaccine and drug delivery through protection of payloads from both metabolism and off-target effects, while facilitating specific delivery of cargo to immune cells. However, evaluation of immune cell nanoparticle targeting is conventionally restricted to monocultured cell line models. We generated human caveolin-1 nanoparticles, termed caveospheres, which were efficiently functionalized with monoclonal antibodies. Using this platform, we investigated CD4+ T cell and CD20+ B cell targeting within physiological mixtures of primary human blood immune cells using flow cytometry, imaging flow cytometry and confocal microscopy. Antibody-functionalization enhanced caveosphere binding to targeted immune cells (6.6 to 43.9-fold) within mixed populations and in the presence of protein-containing fluids. Moreover, targeting caveospheres to CCR5 enabled caveosphere internalization by non-phagocytic CD4+ T cells--an important therapeutic target for HIV treatment. This efficient and flexible system of immune cell-targeted caveosphere nanoparticles holds promise for the development of advanced immunotherapeutics and vaccines.
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3010, Australia and ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Melbourne, Australia.
authors.forename: Joshua J
authors.initials: JJ
authors.lastname: Glass
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia and ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, Parkville, Australia.
authors.forename: Daniel
authors.initials: D
authors.lastname: Yuen
authors.affiliation: Institute for Molecular Bioscience and Centre for Microscopy and Microanalysis, The University of Queensland, St Lucia, QLD 4072, Australia and ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, St Lucia, Australia.
authors.forename: James
authors.initials: J
authors.lastname: Rae
authors.affiliation: Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia and ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, Monash University, Parkville, Australia.
authors.forename: Angus P R
authors.initials: AP
authors.lastname: Johnston
authors.affiliation: Institute for Molecular Bioscience and Centre for Microscopy and Microanalysis, The University of Queensland, St Lucia, QLD 4072, Australia and ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Queensland, St Lucia, Australia.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Parton
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3010, Australia and ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Melbourne, Australia and Melbourne Sexual Health Centre and Department of Infectious Diseases, Alfred Health, Central Clinical School, Monash University, Melbourne, Australia. skent@unimelb.edu.au.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
authors.affiliation: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC 3010, Australia and ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of Melbourne, Melbourne, Australia.
authors.forename: Robert
authors.initials: R
authors.lastname: De Rose
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D016175:B-Lymphocyte Subsets / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D051242:Caveolin 1 / Q000737:chemistry*; D002460:Cell Line; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy; D018613:Microscopy, Confocal; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology
chemical_list: D000911:Antibodies, Monoclonal; C495540:CAV1 protein, human; D051242:Caveolin 1; D004337:Drug Carriers