Pulmonary delivery of cationic gold nanoparticles boost antigen-specific CD4+ T Cell Proliferation

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.