title: Nanoparticle surface charge impacts distribution, uptake and lymph node trafficking by pulmonary antigen-presenting cells.
abstract: Engineered nanoparticles have the potential to expand the breadth of pulmonary therapeutics, especially as respiratory vaccines. Notably, cationic nanoparticles have been demonstrated to produce superior local immune responses following pulmonary delivery; however, the cellular mechanisms of this increased response remain unknown. To this end, we investigated the cellular response of lung APCs following pulmonary instillation of anionic and cationic charged nanoparticles. While nanoparticles of both surface charges were capable of trafficking to the draining lymph node and were readily internalized by alveolar macrophages, both CD11b and CD103 lung dendritic cell (DC) subtypes preferentially associated with cationic nanoparticles. Instillation of cationic nanoparticles resulted in the upregulation of Ccl2 and Cxc10, which likely contributes to the recruitment of CD11b DCs to the lung. In total, these cellular mechanisms explain the increased efficacy of cationic formulations as a pulmonary vaccine carrier and provide critical benchmarks in the design of pulmonary vaccine nanoparticles.
  
  
  BACKGROUND
  Advance in nanotechnology has allowed the production of precise nanoparticles as vaccines. In this regard, pulmonary delivery has the most potential. In this article, the authors investigated the interaction of nanoparticles with various types of lung antigen presenting cells in an attempt to understand the cellular mechanisms. The findings would further help the future design of much improved vaccines for clinical use.
authors.affiliation: Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC, USA.
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Fromen
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Tojan B
authors.initials: TB
authors.lastname: Rahhal
authors.affiliation: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Robbins
authors.affiliation: Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC, USA.
authors.forename: Marc P
authors.initials: MP
authors.lastname: Kai
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: Tammy W
authors.initials: TW
authors.lastname: Shen
authors.affiliation: Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Luft
authors.affiliation: Department of Chemical and Biomolecular Engineering, North Carolina State University, Raleigh, NC, USA; Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Chemistry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. Electronic address: DeSimone@unc.edu.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: DeSimone
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000378:metabolism*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D007477:Ions / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics*; D008168:Lung / Q000378:metabolism*; D008198:Lymph Nodes / Q000378:metabolism*; D016676:Macrophages, Alveolar / Q000378:metabolism; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D013499:Surface Properties; D014612:Vaccines / Q000008:administration & dosage*
chemical_list: D004337:Drug Carriers; D007477:Ions; D014612:Vaccines
keywords: Dendritic cell; Lung; Nanoparticle; Pulmonary drug delivery; Vaccine