Breathe easy: how inhalable nanosensors could enhance lung cancer diagnostics
Researchers have designed inhalable nanosensors for the detection of lung cancer.
Mortality rates for lung cancer have steadily declined in high development index countries due to the rollout of screening programs and advancements in diagnostic tools, which allow for treatment to be provided in the earlier, treatable stages of the disease. However, there is a pressing need to develop more cost-effective diagnostic tools for cancer in low- and middle-income countries, where lung cancer death continues to be disproportionately high.
In this study, researchers from various faculties at the Massachusetts Institute of Technology (MIT; MA, USA) combined inhalable nanosensors with a simple lateral flow test to detect tumor-associated proteolytic signatures.
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The first part of the technique involves activity-based nanosensors being deployed using either an inhaler or a nebulizer. As these nanosensors move throughout the thoracic tissue, they may encounter lung-cancer-associated proteases. The protease acts as a lawnmower, removing DNA reporters from the sensor and shedding them into the systemic circulation. A paper-based lateral flow assay with multiplexing capacity detects the DNA reporters excreted via urine, quantifying their concentration to indicate whether cancerous cells are present.
By utilizing a portable inhaler with a simple lateral flow test, the team have developed a non-invasive technique that could provide a much needed supplement – or even replacement – for current lung cancer diagnostic tools, such as low-dose computed tomography and liquid biopsies. Using machine learning, the researchers have also been able to home in on which nanosensors provide the most accurate results.
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Within earlier stages of testing the sensor, the team utilized mass spectrometry for processing their samples; however, this requires specific analytical equipment, which limits its application in resource-restricted areas. “We were really pushing this assay to be point-of-care available in a low-resource setting, so the idea was to not do any sample processing, not do any amplification, just to be able to put the sample right on the paper and read it out in 20 minutes,” explained senior author Sangeeta Bhatia.
The platform, termed PATROL (point-of-care aerosolizable nanosensors with tumor-responsive oligonucleotide barcodes), has demonstrated both high specificity and sensitivity in detecting early stage lung cancer in a mouse model.
In terms of next steps, the team would like to expand the capability of PATROL from the periphery of tumor nodules into deeper tumor locations by attaching a tumor-penetrating enhancer. They also wish to investigate what other external factors could impact the testing performance of the tool and see if it could be combined with wearable devices to enhance its accessibility. Finally, the researchers are looking to test their diagnostic tool on human biopsy samples, with the ultimate aim of conducting a clinical trial of the sensor.
