Press Release

Imaging

Melanin as a new diagnosis and treatment tool for tumors – Black nanoparticles slow the growth of tumors

The dark skin pigment melanin protects us from the sun’s damaging rays by absorbing light energy and converting it to heat. This could make it a very effective tool in tumor diagnosis and treatment, as demonstrated by a team from Helmholtz Zentrum München and Technical University of Munich (TUM). The scientists managed to create melanin-loaded cell membrane derived nanoparticles, which improved tumor imaging in an animal model while also slowing the growth of the tumor

Infrared thermal images show elevated tumor (yellow) temperature after laser irradiation with OMV-melanin treated (right image). Left with OMVs without melanin. © V. Gujrati/ TUM

Nanoparticles are considered a promising weapon in the fight against tumors due to the fact that tumor tissue absorbs them more readily than healthy cells because their vascular system is more permeable. A good example is provided by outer membrane vesicles (OMVs), which are basically small bubbles surrounded by bacterial membrane. These 20- to 200-nanometer particles are of interest because they are biocompatible, biodegradable and can be easily and inexpensively produced in bacteria, even in large volumes. Once loaded with medicinal active agents, they are easy to administer.

Nanoparticles carrying a black cargo

The huge potential of OMVs in tumor diagnosis and treatment has been demonstrated by Prof. Vasilis Ntziachristos, Director of the Institute of Biological and Medical Imaging (IBMI) at Helmholtz Zentrum München and Professor of Biological Imaging at TUM, and his team. Their work builds on the characteristic properties of OMVs and melanin. Dr. Vipul Gujrati, first author of the study, explains the principle: “Melanin absorbs light very readily – even in the infrared spectrum. We use precisely this light in our optoacoustic imaging technique for tumor diagnosis. It simultaneously converts this absorbed energy into heat, which is then emitted. Heat is also a way to combat tumors – other researchers are currently exploring this method in clinical trials.

Optoacoustics, a method which has been significantly advanced by Ntziachristos, combines the benefits of optical imaging and ultrasound technology. Weak laser pulses gently heat the tissue, causing it to briefly expand very slightly. Ultrasound signals are produced when the tissue contracts again as it cools down. The measured signals vary depending on the tissue type. The scientists record them with special detectors and “translate” them into three-dimensional images. Sensor molecules or probes (such as OMVs) can improve the specificity and accuracy of the technique even further.

Heat build-up reduces tumor growth

The scientists initially had to overcome a problem specific to melanin: It is not very water-soluble and therefore difficult to administer. This is where the OMVs came into play. The researchers engineered bacteria in such a way that they produce melanin and store it in their membrane derived nanoparticles. They then tested the black nanoparticles in tumor tissue, which was excited with infrared laser pulses as part of the optoacoustic procedure.

OMVs proved to be suitable sensor probes for this diagnosis technique because they delivered sharp, high-contrast images of the tumor. They are also well-suited to photothermal therapy approaches, where the tumor tissue is heated with stronger laser pulses in order to kill the cancer cells. The melanin in the nanoparticles caused the temperature of the tumor tissue to rise from 37 °C to up to 56 °C. Control tumors with no melanin only reached a maximum temperature of 39 °C. In the ten days following the treatment, the tumors grew at a significantly slower rate than those in the control group that had not received melanin OMVs. This heat effect was amplified by another positive effect of the particles: By causing a slight non-specific inflammation in the tumor tissue, the immune system was triggered to attack the tumor.

“Our melanin nanoparticles fit into the new medical field of theranostics – where therapy and diagnostics are combined. This makes them a highly interesting option for use in clinical practice,” says Ntziachristos. The scientists will now develop their OMVs further to bring them into clinical use in the future.


Further Informationen

Original Publication:

Vipul Gujrati, Jaya Prakash, Jaber Malekzadeh-Najafabadi, Andre Stiel, Uwe Klemm, Gabriele Mettenleiter, Michaela Aichler, Axel Walch and Vasilis Ntziachristos: Bioengineered bacterial vesicles as biological nanoheaters for optoacoustic imaging, Nature Communications, March 7, 2019, DOI: 10.1038/s41467-019-09034-y

As German Research Center for Environmental Health, Helmholtz Zentrum München pursues the goal of developing personalized medical approaches for the prevention and therapy of major common diseases such as diabetes mellitus, allergies and lung diseases. To achieve this, it investigates the interaction of genetics, environmental factors and lifestyle. The Helmholtz Zentrum München has about 2,500 staff members and is headquartered in Neuherberg in the north of Munich. Helmholtz Zentrum München is a member of the Helmholtz Association, a community of 19 scientific-technical and medical-biological research centers with a total of about 37,000 staff members. 

The Institute of Biological and Medical Imaging (IBMI) conducts research into in vivo imaging technologies for the biosciences. It develops systems, theories and methods of imaging and image reconstruction as well as animal models to test new technologies at the biological, preclinical and clinical level. The aim is to provide innovative tools for biomedical laboratories, for diagnosis and for the therapeutic monitoring of human diseases.

The Technical University of Munich (TUM) is one of Europe’s leading research universities, with around 550 professors, 41,000 students, and 10,000 academic and non-academic staff. Its focus areas are the engineering sciences, natural sciences, life sciences and medicine, combined with economic and social sciences. TUM acts as an entrepreneurial university that promotes talents and creates value for society. In that it profits from having strong partners in science and industry. It is represented worldwide with the TUM Asia campus in Singapore as well as offices in Beijing, Brussels, Cairo, Mumbai, San Francisco, and São Paulo. Nobel Prize winners and inventors such as Rudolf Diesel, Carl von Linde, and Rudolf Mößbauer have done research at TUM. In 2006 and 2012 it won recognition as a German "Excellence University." In international rankings, TUM regularly places among the best universities in Germany.

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