Journal
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
Volume 12, Issue 7, Pages 1815-1826Publisher
ELSEVIER
DOI: 10.1016/j.nano.2016.02.020
Keywords
Gold nanoparticles; Dendritic cell; Macrophage; Respiratory tract; Immune modulation
Funding
- Swiss National Science Foundation [NFP64 406440-131266]
- Adolphe Merkle Foundation
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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. (C) 2016 Elsevier Inc. All rights reserved.
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