Medical imaging plays an important role in the diagnosis of illnesses and the implementation of therapeutic measures. In order to be able to gain detailed information from the human body and generate high-quality images of deeper tissue layers, researchers from the DWI Leibniz Institute for Interactive Materials, the Helmholtz Institute for Biomedical Engineering, and RWTH Aachen University Hospital are conducting research on new types of fluorescent particles.
With the help of these particles, it shall become possible to make pathological tissue visible, among other applications. When applying fluorescence-based imaging techniques, “it is important that these particles are removed from the body once they have fulfilled their purpose,” explains DWI’s Dr. Alexander Kühne. By finding a way how to decompose the fluorescent particles with the help of immune system cells, the researchers have now made an important step towards achieving their goal.
Depending on the medical question or problem at hand, doctors have various tools at their disposal to make organs or tissue in a patient’s body visible. Among these tools are tiny, artificial molecules or particles that can be used as probes. Such particles can reach and attach themselves to pathological tissue via the patient’s bloodstream. These particles can then be localized from outside the body with the help of lasers, supporting doctors to make correct diagnoses and initiate or monitor a suitable treatment.
However, there are still a few obstacles to overcome. Dr. Wiltrud Lederle from RWTH Aachen University Hospital explains that the application of very small probes is problematic, as these are quickly removed by the kidneys. Larger particles, which circulate in the body for longer periods, may accumulate in body cells and adversely affect healthy tissue. Conjugated polymer nanoparticles – special organic macromolecules which emit strong fluorescence –, however, do not harm the body’s cells.
Due to their strong fluorescence, these particles can be detected up to five centimeters into the biological tissue. Furthermore, the polymer particles can be equipped with further functionality. For example, it is possible to add biological components which are capable of detecting and attaching to cells of a particular tumor. In the past, such probes were not applied in medical practice, as there was no way of removing them from the body. Often, such particles are up to one micrometer in size, and the kidney only excretes particles up to about five to six nanometers. Larger particles are taken up by macrophages, that is, cells of the immune system, and finally accumulate in the liver, lung, and spleen, where, in the long run, they may result in undesired side effects.
Nevertheless, the Aachen researchers realized the potential of conjugated polymers for medical imaging, so they sought – and finally found – a solution to the problem: “We succeeded in equipping the conjugated polymers with a kind of predetermined rupture point. To achieve this, we used a certain organic compound, a so-called imidazole ring. The imidazole ring reacts with reactive oxygen species, which can be found within activated macrophages. The researchers were able to demonstrate in cell culture experiments that within the macrophages, the particles were decomposed into small, water-soluble molecules. These can be excreted through the renal system. Lederle concludes: “This bio-degradation process is promising. Now we will continue with further experiments with the aim of making the particles usable for medical imaging applications as well as for the targeted transport of pharmaceuticals within the patient’s body”.
Dr. Janine Hillmer
Leibniz Institute for Interactive Materials (DWI)