title: Pulmonary delivery of cationic gold nanoparticles boost antigen-specific CD4+T Cell Proliferation.
abstract: To address how surface charge affects the fate of potential nanocarriers in the lung, gold nanoparticles (AuNPs) coated with polyvinyl alcohol containing either positively (NH2) or negatively (COOH) charged functional groups were intra-nasally instilled in mice, and their uptake by antigen presenting cell populations (APC) in broncho-alveolar lavage (BAL) fluid, trachea, and lung parenchyma, as well as trafficking to the lung draining lymph nodes (LDLNs) was assessed by flow cytometry. Furthermore, CD4+T cell proliferation in LDLNs was investigated following instillation. All APC subpopulations preferentially captured positively-charged AuNPs compared to their negatively-charged counterparts. Uptake of AuNPs up-regulated expression of co-stimulatory molecules on all APC populations. Furthermore, positively-charged AuNPs induced enhanced OVA-specific CD4+T cell stimulation in LDLNs compared to negatively-charged AuNPs, or polymer alone. Our findings demonstrate surface charge as a key parameter determining particle uptake by APC, and down-stream immune responses depend on the presence of particle core-bound polymer.
authors.affiliation: Respiratory Medicine, Department of Clinical Research, Bern University Hospital, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors.forename: Emilie
authors.initials: E
authors.lastname: Seydoux
authors.affiliation: Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland.
authors.forename: Laura
authors.initials: L
authors.lastname: Rodriguez-Lorenzo
authors.affiliation: Respiratory Medicine, Department of Clinical Research, Bern University Hospital, University of Bern, Bern, Switzerland; Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
authors.forename: Rebecca A M
authors.initials: RA
authors.lastname: Blom
authors.affiliation: School of Veterinary and Life Sciences, Molecular and Biomedical Sciences, Murdoch University, Perth, Australia; Telethon Kids Institute, Perth, Australia.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Stumbles
authors.affiliation: Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland.
authors.forename: Alke
authors.initials: A
authors.lastname: Petri-Fink
authors.affiliation: Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Rothen-Rutishauser
authors.affiliation: Respiratory Medicine, Department of Clinical Research, Bern University Hospital, University of Bern, Bern, Switzerland. Electronic address: fabian.blank@dkf.unibe.ch.
authors.forename: Fabian
authors.initials: F
authors.lastname: Blank
authors.affiliation: Respiratory Medicine, Department of Clinical Research, Bern University Hospital, University of Bern, Bern, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: von Garnier
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D049109:Cell Proliferation; D006046:Gold / Q000008:administration & dosage*; D008168:Lung; D008213:Lymphocyte Activation; D051379:Mice; D053758:Nanoparticles
chemical_list: D006046:Gold
keywords: Dendritic cell; Gold nanoparticles; Immune modulation; Macrophage; Respiratory tract