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Wednesday, 18 July, 2012

One particle - a lot of functions

Smallest siRNA particles possible to date

Nanoparticles can save lives when they target and destroy diseased cells. NIM scientists have developed an exceptionally small particle that is very well equipped for this task.

Nanoparticles are often used as a means of transport in medicine. They are loaded with substances that can switch off selected diseased cells. These compounds include short RNA fragments known as interference RNA (siRNA). After being transported into the interior of the cell, they bind specifically to certain sections of messenger RNA (mRNA), which forms the basis for the synthesis of proteins. In this way artificial siRNA fragments can inhibit the synthesis of specific essential proteins, thus leading to the death of the cell.

Big hopes for a little particle

With modern techniques, these medically desired reactions in the cell interior can now be relatively well controlled by scientists. More difficult, however, is transporting the nanoparticles from the injection site through the bloodstream specifically to the diseased tissue, without incurring losses. The particles must be well equipped for this journey. They need a stable framework and the ability to move unimpeded through the circulatory system. They must also bind exclusively to the target cells and be accepted by them. Lastly, the actual active substance, the siRNA, must be released from the particle.

New record in the world of nanoparticles

Together with his colleagues, NIM scientist Professor Ernst Wagner, Chair for Pharmaceutical Biotechnology at LMU Munich, has developed a new method for producing particles that combine all of these properties. The scientists have produced the smallest siRNA particles possible to date, with a mean diameter of 6 nanometers. “Only the polymer technology recently developed by us enables such feature-rich but still precise packaging for drug transport,” explains Professor Wagner.

The core is formed of positively charged polyamides to which the siRNA molecules are bound. A thin polymer layer prevents unwanted contact with other compounds in the blood. Lastly, the scientists attach two molecules to the surface of the particles: A folic acid molecule that binds with high specificity to tumor cells and a peptide that destroys the vesicle in which the nanoparticles are transported, thus allowing the particles to enter the cell’s interior. Now the siRNA molecules can start their work.

Tumor growth stopped

In a recent test Ernst Wagner and his colleagues switched off a gene that is essential for cell division. This stopped the tumor from growing. The pharmaceutical biotechnologists showed that all the above features are essential for successful treatment. With the developed methods, the particles are stable in vivo for long periods and bind exclusively to the target cells. Another important aspect is that the nanoparticles do not remain in the body but are eliminated through the kidneys. In the test, the scientists demonstrated that the target gene had been switched off. Appropriately confident, Professor Wagner describes the future prospects: “The new technology presented by us is a very encouraging start in the development of new siRNA and other biopharmaceuticals.”

 

Publication

Nanosized Multifunctional Polyplexes for Receptor-Mediated SiRNA Delivery.
Dohmen C, Edinger D, Fröhlich T, Schreiner L, Lächelt U, Troiber C, Rädler J, Hadwiger P, Vornlocher HP, Wagner E. ACS Nano. 2012 Jun 7 (Online-Veröffentlichung).

Contact

Prof. Dr. Ernst Wagner
Pharmaceutical Biotechnology
Center for System-based Drug Research
Department of Pharmacy
Butenandtstraße 5-13, Building D
D- 81377 München

Tel.: 089/2180-77841
E-mail: Ernst.Wagner(at)cup.uni-muenchen.de
Homepage

Picture:
Cell nucleus DNA (blue), divison blocked by siRNA

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Dr. Peter Sonntag
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Phone: +49 (89) 2180 6794

Opens window for sending emailpeter.sonntag(at)lmu.de 

 

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Phone: +49 (89) 2180 5091

Opens window for sending emailisabella.almstaetter(at)physik.uni-muenchen.de

 

 

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