Intratracheally instilled titanium dioxide nanoparticles translocate to heart and liver and activate complement cascade in the heart of C57BL/6 mice

Abstract

An estimated 1% or less of nanoparticles (NPs) deposited in the lungs translocate to systemic circulation and enter other organs; however, this estimation may not be accurate given the low sensitivity of existing in vivo NP detection methods. Moreover, the biological effects of such low levels of translocation are unclear. We employed a nano-scale hyperspectral microscope to spatially observe and spectrally profile NPs in tissues and blood following pulmonary deposition in mice. In addition, we characterized effects occurring in blood, liver and heart at the mRNA and protein level following translocation from the lungs. Adult female C57BL/6 mice were exposed via intratracheal instillation to 18 or 162 µg of industrially relevant titanium dioxide nanoparticles (nano-TiO2) alongside vehicle controls. Using the nano-scale hyperspectral microscope, translocation to heart and liver was confirmed at both doses, and to blood at the highest dose, in mice analyzed 24 h post-exposure. Global gene expression profiling and ELISA analysis revealed activation of complement cascade and inflammatory processes in heart and specific activation of complement factor 3 in blood, suggesting activation of an early innate immune response essential for particle opsonisation and clearance. The liver showed a subtle response with changes in the expression of genes associated with acute phase response. This study characterizes the subtle systemic effects that occur in liver and heart tissues following pulmonary exposure and low levels of translocation of nano-TiO2 from lungs.

Surface modification does not influence the genotoxic and inflammatory effects of TiO2nanoparticles after pulmonary exposure by instillation in mice

“…The TiO 2 NPs are likely to be cleared slowly from lung and to translocate and accumulate slowly (<1% of the instilled dose) in the liver during the 28 days as we have reported previously with another TiO 2 NP (10,11). Both NRCWE-001 and -002 induced increased DNA strand break levels across time points, doses and tissues.…”

“…We have previously assessed TiO 2 NPs and sanding dust from paint with and without nanoparticles using the same experimental set-up (1–3,10,11,17,48). Pulmonary exposure to TiO 2 NPs and sanding dust induced pulmonary inflammation but no genotoxicity (1).…”

Multi-walled carbon nanotube-physicochemical properties predict the systemic acute phase response following pulmonary exposure in mice

“…Although the doses may appear relatively high, occupational CNT exposure concentrations of 30–300 mg/m 3 have previously been reported [64–66]. The doses used were comparable to those of other MWCNT instillation/aspiration studies [7;30;67] and were selected to enable comparisons between both studies and across different ENMs [32;50;68–71]. …”

Nanoparticles in Daily Life: Applications, Toxicity and Regulations

“…31–33 Bioaccumulation, subacute toxicity, and tissue distribution of TiO 2 NPs was exhibited in goldfish ( Carassius auratus ) and C57BL/6 mice. 34,35 …”