In two stages

Nanoparticles in the urine of mice indicated cancer and helped determine its location on PET

Anastasia Kuznetsova, N+1

Researchers from The Massachusetts Institute of Technology has developed a two-stage method for diagnosing malignant tumors. They used nanoparticles that are modified by cancer proteases and in such an altered form are diagnosed in urine. If necessary, positron emission tomography is performed at the second stage, which determines the accumulation of a copper isotope attached to the same nanoparticles in the tumor. The method described in Nature Materials (Hao et al., Microenvironment-triggered multimodal precision diagnostics) makes it possible to diagnose cancer within a few weeks after its occurrence.

If a malignant tumor is found at an early stage, then usually the patient has a better chance of recovery, so researchers are trying to develop new methods for diagnosing cancer. At the same time, the faster and easier such a diagnostic method is, the more likely it will be used in screening. We have already written that scientists from the UK and the USA have tested a way to determine cancer by urine analysis. They constructed nanoparticles of gold, protein and peptide bonds that are recognized by cancer proteins and cut by them. The modified nanoparticles then enter the urine and turn it blue.

The method developed by MIT scientists under the leadership of Sangeeta Bhatia is based on the features of the pathology of malignant tumors: cancer cells usually use proteases – enzymes that allow them to cut the extracellular matrix and spread in the body. The researchers created nanoparticles coated with proteins that are a target for proteases. Such nanoparticles were injected into sick animals, proteases cut the proteins on their surface, and the modified nanoparticles entered the urine, where their presence was determined by enzyme immunoassay. The developed method of diagnosing malignant tumors made it possible to detect lung cancer in mice as early as five weeks after its occurrence.

After the success of the first stage of the study, the scientists set themselves a new task – to understand exactly where the tumor is located in the body of mice. To do this, they added a protein (pH-Low Insertion Peptid) to the developed nanoparticles, which is attracted to tissues with an acidic environment. Nanoparticles cluster around tumors, as cancer cells make the environment around them acidic. The ⁶⁴ Cu copper isotope was also added to the nanoparticles, which can be determined by positron emission tomography.

The researchers tested their diagnostic method on mice with lung and liver cancer and were able to track how the signal from the isotope changes during treatment. The whole experiment took less than a month: a week after the tumor appeared, a urine test already showed its presence, the mice immediately began treatment with 5-fluorouracil, and two weeks later (3 weeks in the case of liver cancer), according to the results of positron emission tomography, the condition of the animals improved significantly.

Visualization of the tumor using PET. Figure from the article by Hao et al.

This diagnostic method can be useful for screening studies. At the first stage, according to the urine analysis, doctors will determine whether a person has cancer, and at the second stage, if the test reveals a tumor, you can immediately apply positron emission tomography to find out its position. This will allow you to diagnose malignancies at an early stage, and begin immediate treatment.

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