title: Aerosol Delivery of Functionalized Gold Nanoparticles Target and Activate Dendritic Cells in a 3D Lung Cellular Model.
abstract: Nanocarrier design combined with pulmonary drug delivery holds great promise for the treatment of respiratory tract disorders. In particular, targeting of dendritic cells that are key immune cells to enhance or suppress an immune response in the lung is a promising approach for the treatment of allergic diseases. Fluorescently encoded poly(vinyl alcohol) (PVA)-coated gold nanoparticles, functionalized with either negative (-COO-) or positive (-NH3+) surface charges, were functionalized with a DC-SIGN antibody on the particle surface, enabling binding to a dendritic cell surface receptor. A 3D coculture model consisting of epithelial and immune cells (macrophages and dendritic cells) mimicking the human lung epithelial tissue barrier was employed to assess the effects of aerosolized AuNPs. PVA-NH2AuNPs showed higher uptake compared to that of their -COOH counterparts, with the highest uptake recorded in macrophages, as shown by flow cytometry. None of the AuNPs induced cytotoxicity or necrosis or increased cytokine secretion, whereas only PVA-NH2AuNPs induced higher apoptosis levels. DC-SIGN AuNPs showed significantly increased uptake by monocyte-derived dendritic cells (MDDCs) with subsequent activation compared to non-antibody-conjugated control AuNPs, independent of surface charge. Our results show that DC-SIGN conjugation to the AuNPs enhanced MDDC targeting and activation in a complex 3D lung cell model. These findings highlight the potential of immunoengineering approaches to the targeting and activation of immune cells in the lung by nanocarriers.
authors.forename: Kleanthis
authors.identifier: 0000-0002-7082-9493
authors.initials: K
authors.lastname: Fytianos
authors.forename: Savvina
authors.initials: S
authors.lastname: Chortarea
authors.forename: Laura
authors.initials: L
authors.lastname: Rodriguez-Lorenzo
authors.affiliation: Respiratory Medicine, Inselspital, University of Bern , 3012 Bern, Switzerland.
authors.forename: Fabian
authors.initials: F
authors.lastname: Blank
authors.affiliation: Respiratory Medicine, Inselspital, University of Bern , 3012 Bern, Switzerland.
authors.forename: Christophe
authors.initials: C
authors.lastname: von Garnier
authors.forename: Alke
authors.initials: A
authors.lastname: Petri-Fink
authors.forename: Barbara
authors.initials: B
authors.lastname: Rothen-Rutishauser
mesh_terms: D000336:Aerosols / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D016503:Drug Delivery Systems; D006046:Gold / Q000737:chemistry* / Q000494:pharmacology; D064368:Healthy Volunteers; D006801:Humans; D008168:Lung / Q000187:drug effects*; D053768:Metal Nanoparticles / Q000737:chemistry*; D008954:Models, Biological; D009000:Monocytes / Q000166:cytology; D010316:Particle Size; D013499:Surface Properties
chemical_list: D000336:Aerosols; D004337:Drug Carriers; D006046:Gold
keywords: aerosol exposures; cellular uptake; dendritic cells; gold nanoparticles; immunomodulation