“Inhaled” test for lung cancer – 2024-02-19 15:54:43

Inhale, pee, done! And in 20 minutes in this simple, non-invasive way you will be able to receive a very accurate diagnosis of the possible existence of lung cancer at an early stage. This is the diagnostic future against one of the most frequent and deadly cancers of our modern world (but also against other respiratory diseases) which is being “built” inside the Massachusetts Institute of Technology (MIT).

A future based on the innovative PATROL test that actually… patrols the lungs looking for cancer through the use of nanoparticles covered with sensors that recognize the presence of proteins that are only produced by lung cancer cells. When the sensors detect such proteins they produce a signal that accumulates in the urine and can be detected by a simple test based on a paper strip.

Nanoparticles and barcodes

As mentioned in “Vima” o Qian Zhongresearcher at MIT and first author of the relevant study which was recently published in the scientific journal “Science Advances”, “The new approach could replace or complement the examination that is currently considered the gold standard for the early diagnosis of lung cancer, Low Dose CT. Such a simple and easy-to-use test, which we estimate will be lower-cost compared to computed tomography, could be of significant help in areas where CT scanners are not widely available.”

The other first author of the study dr Edward Tana former postdoctoral researcher at MIT, described to Vima exactly how the easy-to-use system works: “The sensors we use consist of polymer nanoparticles covered with a marker – a DNA barcode – which is cleaved from the nanoparticle when the sensor encounters enzymes, called proteases, that are overactive in tumors. These benchmarks eventually accumulate in the urine.”

Results in 20 minutes

Nanoparticles can be administered in two forms: either as a solution that is made into an aerosol and administered by a nebulizer, or as a dry powder that is administered via an inhaler. Once they reach the lungs, they penetrate the tissue where they encounter as many proteases as are present. Dr. Zhong explained that human cells express hundreds of different proteases, some of which are overactive in tumors and help cancer cells migrate away from the original cancer site by acting as “knives” that cut through extracellular matrix proteins. “Proteases cleave the DNA barcodes from the sensors and allow them to enter the bloodstream until they are excreted in the urine.”

But how are benchmarks analyzed? Through a… paper test. The research team designed a special film that detects four different DNA ‘barcodes’ each of which indicates the presence of a different protease – the scientists arrived at these four markers using a machine learning algorithm. Dr. Zhong noted that “no processing of the urine sample is required prior to analysis, and results are available in approximately 20 minutes.”

PATROL was tested in mice genetically engineered to develop human-like lung adenocarcinoma tumors. The nanoparticles were administered 7.5 weeks after the tumors began to grow, a time point that corresponds to stage 1 or 2 cancer in humans. As Dr. Zhong informed us “based on the findings, the sensitivity of the test was over 80%, which is comparable to the accuracy of low-dose computed tomography today.” We asked the researchers if more proteases would be needed to be analyzed in humans to make an accurate diagnosis. Dr. Zhong replied that “Given that cancer is a very heterogeneous disease, we expect that a complex panel of sensors will be needed to identify more protein targets compared to those identified in our preclinical models.”

The next step for the team is to analyze samples from human biopsies to discover the right panel of sensors to detect human lung tumors. Their goal is also to apply this approach to the detection of other respiratory diseases, emphasized Dr. Tan. “This particular platform can be adapted to detect other respiratory diseases such as infections. We also aim to apply the new technology to monitor the progression of respiratory diseases, mainly in terms of patients’ response to different treatments.”

MIT’s nano-sensors for other diseases as well

This particular MIT research group, led by Health Sciences and Technology and Department of Electrical Engineering and Computer Science Professor Sangita Bhatia, has been developing nano-sensors for the diagnosis of different diseases for years. He has already created such nano-sensors for the diagnosis of liver and ovarian cancer, but in those cases the nanoparticles were administered intravenously. In fact, a company called Sunbird Bio has conducted a small phase I clinical trial with a similar sensor developed in the MIT lab to diagnose liver cancer and a form of hepatitis called non-alcoholic steatohepatitis (NASH – chronic inflammation of the liver or which is caused in people with steatosis, i.e. fat deposition in the liver). Some early results on testing nano-sensors in the diagnosis of NASH were published in 2021 in Science Translational Medicine. In this particular case the research team developed the GBTS system (Glympse Bio Test System) which, following the same logic as that followed for the diagnosis of lung cancer, looked for liver proteases. A panel of 13 proteases was generated and tested in NASH mice. As it turned out, the system was able to separate NASH from simple steatosis as well as from healthy tissue in the experimental animals and also show how the therapeutic intervention led to a remission of the condition.