Deep breath and subsequent urine test instead of complicated tests: Researchers have developed an uncomplicated procedure for diagnosing early lung cancer. The biodegradable nanosensors 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. Scientists say successful tests on mice so far give hope that the concept will develop into a readily available alternative to more sophisticated detection methods.
Early detection is the key to success: For many types of cancer, there are now good chances of cure if the disease is detected at an early stage of development. This also applies to one of the most common oncological diseases worldwide: lung cancer. Until now, computed tomography (CT) scans have been used for early diagnosis of this disease. However, this is a very complex process and requires expensive equipment and skilled personnel.
For this reason, CT scans are often not available to people in some parts of the world. In addition, an incorrect diagnosis can often occur with this procedure, leading to unnecessary follow-up examinations. “In our development work, we aimed to provide a method that can detect lung cancer with a high degree of specificity and sensitivity while lowering the accessibility threshold,” says first author Qian Zhong of the Massachusetts Institute of Technology in Cambridge.
Detect tumors intelligently
The solution concept that Zhong and his colleagues are now presenting is based on specially designed nanosensors that can be inhaled in the form of a mist via an inhaler. The small pieces consist of an easily biodegradable polymer base structure to which 'reporter DNA' molecules are attached via specific protein linkers. Once the particles reach the lungs, they are absorbed into the tissues and hit any tumor tissue that may be present. Nanosensors can recognize it by a distinct property: Cancerous tissue releases specific enzymes that break down proteins. These so-called proteases help proliferating cells, among other things, to establish themselves in the body by severing tissue structures.
Researchers have now engineered the connections between the core structure of the particles and the tRNA molecules so that they are specifically cut by typical tumor proteases. The separated reporter DNA molecules can then enter the bloodstream, where the kidneys eventually filter out these molecules and release them into the urine. They can then be detected using a test strip containing specific binding partners for the reporter DNA molecules. No pretreatment or preparation of the urine sample is required, and results can be read about 20 minutes after the sample is taken, the researchers reported.
Promising test results
To test whether the system delivers what it promises, Zhong and his team conducted studies on specially developed breeding strains of mice that develop lung tumors similar to those found in humans. The sensors were administered to these animals by inhalation approximately seven weeks after tumor formation began. Scientists explain that the timing corresponds to an early stage of cancer development in humans. In their first series of experiments, they recorded the values of 20 different sensors that detect different proteases. The researchers reported that a combination of four sensors then appeared to be optimal: in a mouse model, they were able to detect early-stage lung tumors with a high success rate.
Following these promising results, they now want to explore possible uses of the diagnostic system in humans. Zhong and his colleagues initially plan to conduct studies on human tissue samples to see if the sensor array 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 achieve their goal: providing an accurate yet uncomplicated technology for early lung cancer detection that can also reach previously underserved populations in the world.
Source: Massachusetts Institute of Technology, specialized article: Scientific Progress, doi: 10.1126/sciadv.adj9591
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