Aerosol Delivery of Functionalized Gold Nanoparticles Target and Activate Dendritic Cells in a 3D Lung Cellular Model.

Fytianos, Kleanthis; Chortarea, Savvina; Rodriguez-Lorenzo, Laura; Blank, Fabian; Von Garnier, Christophe; Petri-Fink, Alke; Rothen-Rutishauser, Barbara (2017). Aerosol Delivery of Functionalized Gold Nanoparticles Target and Activate Dendritic Cells in a 3D Lung Cellular Model. ACS nano, 11(1), pp. 375-383. American Chemical Society 10.1021/acsnano.6b06061

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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-NH2 AuNPs 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-NH2 AuNPs 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gastro-intestinal, Liver and Lung Disorders (DMLL) > Clinic of Pneumology
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Forschungsbereich Mu50 > Forschungsgruppe Pneumologie (Erwachsene)
09 Interdisciplinary Units > Microscopy Imaging Center MIC
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DCR Services > Core Facility Live Cell Imaging (LCI)

UniBE Contributor:

Blank, Fabian and Von Garnier, Christophe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1936-0851

Publisher:

American Chemical Society

Language:

English

Submitter:

Rahel Holderegger

Date Deposited:

16 Jan 2017 08:48

Last Modified:

19 Feb 2019 14:51

Publisher DOI:

10.1021/acsnano.6b06061

PubMed ID:

27973764

Uncontrolled Keywords:

aerosol exposures; cellular uptake; dendritic cells; gold nanoparticles; immunomodulation

BORIS DOI:

10.7892/boris.93086

URI:

https://boris.unibe.ch/id/eprint/93086

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