A 'spray' to trigger a process that could lead to detect lung cancer early. This is the strategy being worked on by a team of researchers from MIT (Massachusetts Institute of Technology): inhalable nanosensors, which can be delivered by an inhaler or a nebulizer. If these smart particles encounter tumor-related proteins, they produce a signal that accumulates in the urine, where it can be detected with a simple test, such as those performed with a test paper strip.
The approach, based on a new technology developed at MIT, could potentially replace or integrate the current gold standard for the diagnosis of lung cancer, i.e. low-dose computed tomography (CT), the experts suggest by presenting the results of their work published in the journal 'Science Advances'. Mission: make diagnosis as easy as using a spray. This could have a particularly significant impact in low- and middle-income countries that do not have widespread availability of CT machines, they reflect. “Across the world, cancer will become increasingly prevalent in low- and middle-income countries. The epidemiology of lung cancer is linked to pollution and smoking, so we know these are environments where accessibility to this type of technology could have a big impact,” says Sangeeta Bhatia, senior author of the study (which has Qian Zhong and Edward Tan as lead authors).
Bhatia has spent the last decade developing nanosensors for use in the diagnosis of cancer and other diseases, and in this study, she and her colleagues explored the possibility of using them as a more accessible alternative to CT screening for lung cancer. These sensors are made up of polymeric nanoparticles coated with a sort of DNA 'barcode', which is detached from the particle when the sensor encounters enzymes called proteases, which are often overactive in tumors. These barcodes eventually accumulate in the urine and are eliminated from the body.
Previous versions of the sensors, which targeted other tumor sites such as the liver and ovaries, were designed to be administered intravenously. For lung cancer diagnosis, the researchers wanted to create a version that could be inhaled, which could make it easier to implement in lower-resource settings. “When we developed this technology, our goal” was “also to lower the threshold of accessibility, in a way that will hopefully improve resource disparity and inequity in the early detection of lung cancer,” Zhong notes. Two formulations were thus created: a solution that can be aerosolized and administered with a nebulizer, and a dry powder that can be administered using an inhaler.
Once the particles reach the lungs, they are absorbed into the tissues, where they encounter any proteases that may be present. Human cells can express hundreds of different proteases, and some of them are overactive in tumors. These cancer-causing proteases cleave the barcodes from the sensors, allowing them to circulate in the bloodstream until they are excreted in the urine. In previous versions of this technology, researchers used mass spectrometry to analyze the urine sample. In the new version they created a lateral flow test, which allows you to detect barcodes using a simple paper test strip designed to detect up to 4 different DNA barcodes, each indicating the presence of a different protease. “The idea was to be able to put the sample directly on the paper and read it in 20 minutes,” says Bhatia.
The researchers tested their diagnostic system on mice genetically engineered to develop lung tumors similar to those seen in humans. The sensors were administered 7.5 weeks after the tumors began to form, a time point that would likely correlate with stage 1 or 2 cancer in humans. The combination of the 4 that could provide accurate diagnostic results was tested and found that it could accurately detect early-stage lung cancers. For use in humans, more sensors may be needed for an accurate diagnosis, but it could be achieved by using more test paper strips, say researchers who now plan to analyze human biopsy samples to see if the sensor panels they are using they would work. In the long term, they hope to run clinical trials on patients. “The idea would be to get an answer on whether or not a follow-up test is needed, and we could enter patients who have early injuries into the system so they can receive curative surgery or life-saving drugs,” concludes Bhatia.
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