Respiratory epithelial cytotoxicity and membrane damage (holes) caused by amine-modified nanoparticles

Abstract

The respiratory epithelium is a significant target of inhaled, nano-sized particles, the biological reactivity of which will depend on its physicochemical properties. Surface-modified, 50 and 100 nm, polystyrene latex nanoparticles (NPs) were used as model particles to examine the effect of particle size and surface chemistry on transformed human alveolar epithelial type 1-like cells (TT1). Live images of TT1 exposed to amine-modified NPs taken by hopping probe ion conductance microscopy revealed severe damage and holes on cell membranes that were not observed with other types of NPs. This paralleled induction of cell detachment, cytotoxicity and apoptotic (caspase-3/7 and caspase-9) cell death, and increased release of CXCL8 (IL-8). In contrast, unmodified, carboxyl-modified 50 nm NPs and the 100 nm NPs did not cause membrane damage, and were less reactive. Thus, the susceptibility and membrane damage to respiratory epithelium following inhalation of NPs will depend on both surface chemistry (e.g., cationic) and nano-size.

Keywords::

• Nano-scale imaging
• alveolar epithelial
• nanotoxicity
• amine-modified nanoparticles
• cell membrane damage

Author contributions

T.D.T conceived and designed the project. P.R. and P.N. designed and performed experiments. P.R. performed particle characterization and bio-molecular studies. D.B. and E.V. contributed material characterization. HPICM studies were guided by J.G. and Y.E.K. and performed by P.N. The manuscript was written by P.R., with substantial contributions by T.D.T, P.N. and A.J.T. All authors discussed the results and commented on the manuscript.

Acknowledgements

We thank Dr Andrew V. Rogers for proficient assistance with electron microscopy.

Declaration of interest: This research was supported by Medical Research Council of United Kingdom (MRC), grant G0700926, and the NIHR Respiratory Disease Bio-medical Research Unit at the Royal Brompton and Harefield NHS Foundation Trust and Imperial College London. The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.