Enrichment of immunoregulatory proteins in the biomolecular corona of nanoparticles within human respiratory tract lining fluid

Nanomedicine. 2016 May;12(4):1033-1043. doi: 10.1016/j.nano.2015.12.369. Epub 2016 Jan 6.

Abstract

When inhaled nanoparticles deposit in the lungs, they transit through respiratory tract lining fluid (RTLF) acquiring a biomolecular corona reflecting the interaction of the RTLF with the nanomaterial surface. Label-free snapshot proteomics was used to generate semi-quantitative profiles of corona proteins formed around silica (SiO2) and poly(vinyl) acetate (PVAc) nanoparticles in RTLF, the latter employed as an archetype drug delivery vehicle. The evolved PVAc corona was significantly enriched compared to that observed on SiO2 nanoparticles (698 vs. 429 proteins identified); however both coronas contained a substantial contribution from innate immunity proteins, including surfactant protein A, napsin A and complement (C1q and C3) proteins. Functional protein classification supports the hypothesis that corona formation in RTLF constitutes opsonisation, preparing particles for phagocytosis and clearance from the lungs. These data highlight how an understanding of the evolved corona is necessary for the design of inhaled nanomedicines with acceptable safety and tailored clearance profiles.

From the clinical editor: Inhaled nanoparticles often acquire a layer of protein corona while they go through the respiratory tract. Here, the authors investigated the identity of these proteins. The proper identification would improve the understanding of the use of inhaled nanoparticles in future therapeutics.

Keywords: Nanoparticle; Plasma; Poly(vinyl) acetate; Protein corona; Proteomics; Respiratory tract lining fluid; Silica.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aspartic Acid Endopeptidases / biosynthesis
  • Aspartic Acid Endopeptidases / isolation & purification
  • Body Fluids / metabolism
  • Complement C1q / biosynthesis
  • Complement C1q / isolation & purification
  • Complement C3 / biosynthesis
  • Complement C3 / isolation & purification
  • Drug Delivery Systems*
  • Female
  • Gene Expression Regulation / drug effects
  • Humans
  • Male
  • Nanoparticles / administration & dosage*
  • Nanoparticles / adverse effects
  • Protein Corona*
  • Proteomics
  • Pulmonary Surfactant-Associated Protein A / biosynthesis
  • Pulmonary Surfactant-Associated Protein A / isolation & purification
  • Respiratory System / drug effects
  • Respiratory System / metabolism*
  • Silicon Dioxide / administration & dosage
  • Silicon Dioxide / chemistry

Substances

  • Complement C3
  • Protein Corona
  • Pulmonary Surfactant-Associated Protein A
  • Silicon Dioxide
  • Complement C1q
  • Aspartic Acid Endopeptidases
  • NAPSA protein, human