Inhalable nano-detectives find lung cancer

The diagnostic particles can be inhaled as an aerosol. Below you can see these nano-sensors in an electron microscope image. © MIT researchers

A deep breath and a subsequent urine test instead of complex examinations: Researchers have developed an uncomplicated procedure for early lung cancer diagnosis. Biodegradable nano-sensors are inhaled into the lungs through an inhaler. If they encounter tumor tissue there, reporter DNA molecules are released, which then end up in the urine and can be detected using a simple paper test strip test. The successful tests on mice so far give hope that the concept could develop into a readily available alternative to more complicated detection methods, say the scientists.

Early detection is the key to success: For many types of cancer, there are now good chances of recovery if the disease is detected at an early stage of development. This also applies to one of the most widespread tumor diseases worldwide: lung cancer. To date, examinations using computer tomography (CT) have been used for the early diagnosis of this disease. However, this is a quite complex process that requires expensive equipment and skilled personnel.

This is why CT scans are often not available to people in some parts of the world. In addition, incorrect diagnoses can occur relatively often with this procedure, leading to unnecessary, invasive follow-up examinations. “In our development work, we therefore aimed to provide a method that can detect lung cancer with high specificity and sensitivity while lowering the threshold for accessibility,” says first author Qian Zhong from the Massachusetts Institute of Technology in Cambridge.

Tumors cleverly detected

The solution concept that Zhong and his colleagues are now presenting is based on specially designed nano-sensors that can be inhaled in aerosol form via an inhaler. The tiny pieces consist of an easily degradable polymer base structure to which “reporter DNA” molecules are linked via certain protein connections. As soon as the particles reach the lungs, they are absorbed into the tissue and hit any tumor tissue that may be present. The nano-sensors can recognize it by a characteristic feature: the cancer tissue releases certain enzymes that break down proteins. These so-called proteases help the proliferating cells, among other things, to establish themselves in the body by cutting tissue structures.

The researchers have now designed the connections between the basic structure of the particles and the reporter DNA molecules so that they are specifically cut by tumor-typical proteases. The separated reporter DNA molecules can then enter the bloodstream, from which the kidneys ultimately filter them out and release them into the urine. They can then be detected using a test strip that contains specific binding partners for the reporter DNA molecules. No pretreatment or preparation of the urine sample is required and the results can be read about 20 minutes after the sample was taken, the researchers report.

Promising test results

To test whether the system delivers what it promises, Zhong and his team conducted studies on specially developed breeding lines of mice that develop lung tumors similar to those in humans. The sensors were administered to these animals by inhalation approximately seven weeks after the start of tumor formation. The scientists explain that the timing corresponds to an early stage of human cancer development. In their first series of experiments, they recorded the values ​​of 20 different sensors that detect different proteases. A combination of four sensors then emerged as optimal: In the mouse model, they were able to detect early-stage lung tumors with a high success rate, the researchers report.

After these promising results, they now want to explore the possible uses of the diagnostic system in humans. Zhong and his colleagues initially plan to carry out studies on human tissue samples to find out whether the sensor combination they used can also be used in this case. They then hope to soon be able to conduct clinical studies on patients in order to further pursue their goal: to provide a precise and at the same time uncomplicated technology for lung cancer early detection that can also reach previously underserved populations in the world.

Source: Massachusetts Institute of Technology, specialist article: Science Advances, doi: 10.1126/sciadv.adj9591

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