How many inhaled nanoparticles are deposited in the lungs and then translocated into the human body, and what is their biological effect (focus on oxidative stress)? The fate of nanoparticles studied by collecting exhaled breath condensate, blood and urine of volunteers exposed to different types of nanoparticles.
Background
Nanoparticles (NPs) are very interesting for medical and technical applications. Nevertheless, their ability to translocate into the human body (due to their small size) and their increased reactivity (due to their large surface area) may also pose a health risk. Nanomedicine and nanotoxicology currently lack precise information about the actual deposited dose after inhalation of NPs, their fate in the human body and their ability to induce biological effects, such as oxidative stress.
Aim
We hypothesise that i) inhaled NPs deposit in the lung, become suspended in lung lining fluid and subsequently translocate into the bloodstream and ii) only reactive particles initiate oxidative stress in the lung lining fluid, which is followed by an increase in biomarkers of oxidative stress in the bloodstream and urine. The validity of these two hypotheses will be addressed through:
- the development of a method for detecting and measuring fluorescent superparamagnetic iron oxides (SPIONs) in exhaled breath condensate (surrogate of the deposited dose) and in blood and urine of volunteers.
- applying these methodologies to volunteers exposed to reactive (tobacco smoke) and non reactive (SPIONs) particles to demonstrate the appearance of oxidative stress biomarkers as well as to study their temporal evolution and their repartition in the three biological matrices of interest.
Significance
We still lack a full understanding of the chain of events linking the initial deposition of particles in the lung to their health effects. The methodology developed will allow for a non-invasive evaluation of the inhaled NP target dose. Such information is important for substance-oriented human health risk analysis as well as for the development of therapeutic applications. In addition, the time dependent changes of oxidative stress biomarkers in blood and urine will be related to this target dose, allowing for a better understanding of the sequence of systemic effects resulting from pulmonary exposure to NPs.
Original title: Nanoparticle tracking and oxidative stress biomarkers in healthy non-smoking volunteers
Grant: CHF 350’000.-
Duration: 36 months
Project leader
- Dr. Michael Riediker