MIT nanoparticles tag proteins to reveal disease via the breath
Using the breath to gauge the health of our lungs and reveal diseases related to them is emerging as a diagnostic tool with huge potential, with a number of promising technologies on the horizon. Joining them is a new type of nanoparticle developed at MIT that deposits volatile molecules onto proteins linked to various diseases, to act as synthetic biomarkers and reveal signs of pneumonia and other lung conditions in exhaled breath.
The research actually builds on previous work carried out by scientists in the lab of biological engineer Sangeeta N. Bhatia, who earlier this year demonstrated a urine test that could reveal biomarkers of lung cancer. The technology consists of nanoparticles coated in certain peptides that interact with proteins called proteases that are linked to a range of diseases.
The proteases cleave the peptides off of the nanoparticles, which are then excreted via urine to reveal the presence of certain diseases. By modifying the peptide coating of the nanoparticles, they can be customized to react with proteases associated with different diseases, with the team previously using this approach to detect early signs of pneumonia, along with ovarian and colon cancer, also via the urine.
Through continued experiments, the team has now adapted the technology so that it can be used to reveal disease through the breath. This involved further chemical tweaking of the peptides and the attachment of volatile molecules, which enable the nanoparticles to release gases called hydrofluoroamines, which can be detected in exhaled breath.
Using mouse models of bacterial pneumonia and a genetic lung disorder called alpha-1 antitrypsin deficiency, the researchers were able to detect the diseases in the breath via mass spectrometry. They did so by looking for activity of a protease called neutrophil elastase, which is produced by the immune cells in both diseases and could be detected within around 10 minutes. The researchers also demonstrated that the technique could be used to monitor the effectiveness of drug treatments for both diseases.
The team hopes to build on these promising results by making further improvements to the breath-monitoring technology. For example, the nanoparticles are currently injected directly into the trachea of the mice, but the researchers are working on versions that could be inhaled with a device akin to an asthma inhaler. They also hope to develop sensors that can detect more than one type of protease at a time, but will need to carry out more safety testing before applying the technology to humans, though no signs of toxicity were detected in the lungs of the mice.
“We envision that this technology would allow you to inhale a sensor and then breathe out a volatile gas in about 10 minutes that reports on the status of your lungs and whether the medicines you are taking are working,” says Bhatia.
The research was published in the journal Nature Nanotechnology.