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Nano-dwarves turn tumor assassins

Abstract:
Chemotherapy is often preferred for fighting cancer, but its side effects can be considerable. A new technique may reduce these in future: nanoparticle-encapsulated substances could kill off tumor cells selectively. This will be easier on patients.

Nano-dwarves turn tumor assassins

Muenchen, Germany | Posted on October 25th, 2013

Hair loss, nausea, vomiting, fatigue, loss of appetite, loss of eye lashes and eye brows, susceptibility to infection - the list of possible side effects from chemotherapy is lengthy. Many cancer patients suffer from the intense effects that accompany the treatment. High dosages of cytostatic agents are injected subcutaneously or administered intravenously to halt the growth of tumors and also to destroy resistant cells. The more frequently that cells divide, the more effective the active agent is. This applies especially to malignant tumors. However, healthy mucosal tissue and hair cells divide very rapidly as well. They are therefore attacked as well. Scientists have searched long and hard for a therapy that selectively kills off the tumor cells without damaging healthy tissue. Using a new methodology, researchers from the Fraunhofer Institute for Applied Polymer Research (IAP) in Potsdam, Germany, hope to break the vicious circle by utilizing nanoparticles as vehicles for the anti-cancer agents. Since the particles resemble cells on account of their structure, they are suited to steering pharmaceutical substances to the tumor selectively, docking there, and efficiently eliminating the malignant cells.

The researchers have decided to use hydrophobic, water-insoluble lipid vesicles as the tiny, 200-250 nanometer pharmaceutical carriers. They are biologically degradable and disintegrate in the body after deployment. Polymers are used to stabilize the nano-envelope, which is furnished with molecules highly specific to and recognized by tumor cells. The envelope of the nanoparticle - experts call it the vesicles - is constructed similarly that of a cell. The scientists load these carriers with doxorubicin, one of the anti-cancer agents frequently used in chemotherapy. Sodium tetradecyl sulfate (STS), a surfactant, helps the active agent to be absorbed better.

The researchers have already been able to prove the efficacy of their approach in laboratory tests. "We utilized both a cervical cancer strain (HeLa) and cancer of the large intestine (HCT116) for our in-vitro tests. They each react very differently to doxorubicin. HCT116 cells are sensitive to the substance, in contrast to HeLa cells. We ran the experiments with pharmacologically relevant dosages, used by clinicians. The doxorubicin was added to the cell cultures both directly and encapsulated in the nano-carriers," explains Dr. Joachim Storsberg. He developed the new therapy jointly with Dr. Christian Schmidt and Nurdan Dogangüzel from IAP in close collaboration with colleagues from the pharmaceutical sciences, Prof. Mont Kumpugdee-Vollrath and Dr. J. P. Krause from Beuth University of Applied Sciences in Berlin.

Making chemotherapy more tolerable

The results from the laboratory tests: after three days, 43.3 percent of the HeLa cells survived a dose of unencapsulated, 1 micromolar (µM) doxorubicin. When the active agent was introduced via encapsulated vesicles, only 8.3 percent of the malignant HeLa cells survived. "The pharmaceutical substance in the nano-envelopes was fives times more effective," says Storsberg. This could also be observed in the tests with the intestinal cancer cells: in this experiment, 46.5 percent of the HCT116 cells survived a dose of 0.1 µM doxorubicin after two days, while only 13.3 percent of the malignant tumor cells failed to be eliminated by administering the active agent in encapsulated form. "With nanoparticles as carriers, a more effective and simultaneously lower dosage is possible. This way, and with a targeted delivery of the active agent, the healthy cells are are likely to be spared and the side effects will be minimized," says Storsberg. An additional test result: the encapsulation material is only effective when combined with the active agent. The unloaded nano-carrier does not attack the sensitive HCT116 cells. Using their methodology, Storsberg and his team can investigate how effectively an encapsulated pharmaceutical substance acts, as well as how ‘toxic' the actual nanomaterial is. "That has not been feasible to date," emphasized the chemist.

The researchers will be presenting their results at Nanotech Dubai, 28-30 October 2013. However, a series of clinical tests with cancer patients will only be set up if these observations are confirmed in in-vivo experiments.

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About Fraunhofer-Gesellschaft
The Fraunhofer-Gesellschaft is the leading organization for institutes of applied research in Europe, undertaking contract research on behalf of industry, the service sector and the government. Commissioned by customers in industry, it provides rapid, economical and immediately applicable solutions to technical and organizational problems. Within the framework of the European Union's technology programs, the Fraunhofer-Gesellschaft is actively involved in industrial consortiums which seek technical solutions to improve the competitiveness of European industry.

Research of practical utility lies at the heart of all activities pursued by the Fraunhofer-Gesellschaft. Founded in 1949, the research organization undertakes applied research that drives economic development and serves the wider benefit of society. Its services are solicited by customers and contractual partners in industry, the service sector and public administration. The organization also accepts commissions from German federal and Laender ministries and government departments to participate in future-oriented research projects with the aim of finding innovative solutions to issues concerning the industrial economy and society in general.

Applied research has a knock-on effect that extends beyond the direct benefits perceived by the customer: Through their research and development work, the Fraunhofer Institutes help to reinforce the competitive strength of the economy in their local region, and throughout Germany and Europe. They do so by promoting innovation, accelerating technological progress, improving the acceptance of new technologies, and not least by disseminating their knowledge and helping to train the urgently needed future generation of scientists and engineers.

As an employer, the Fraunhofer-Gesellschaft offers its staff the opportunity to develop the professional and personal skills that will allow them to take up positions of responsibility within their institute, in other scientific domains, in industry and in society. Students working at the Fraunhofer Institutes have excellent prospects of starting and developing a career in industry by virtue of the practical training and experience they have acquired.

At present, the Fraunhofer-Gesellschaft maintains more than 80 research units, including 56 Fraunhofer Institutes, at 40 different locations in Germany. The majority of the 12,500 staff are qualified scientists and engineers, who work with an annual research budget of €1.2 billion. Of this sum, more than €1 billion is generated through contract research. Two thirds of the Fraunhofer-Gesellschaft’s contract research revenue is derived from contracts with industry and from publicly financed research projects. Only one third is contributed by the German federal and Laender governments in the form of institutional funding, enabling the institutes to work ahead on solutions to problems that will not become acutely relevant to industry and society until five or ten years from now.

Affiliated research centers and representative offices in Europe, the USA and Asia provide contact with the regions of greatest importance to present and future scientific progress and economic development.

The Fraunhofer-Gesellschaft is a recognized non-profit organization which takes its name from Joseph von Fraunhofer (1787-1826), the illustrious Munich researcher, inventor and entrepreneur.

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Contacts:
Joachim Storsberg
Fraunhofer Institute for Applied Polymer Research IAP
+49 331 568-1321

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