Researchers have Developed Stable Nano-Packaging for Medicines

Medicines often have undesirable side effects. One reason for this is that they not only reach sick but also healthy cells and act on them. Researchers at the Technical University of Munich (TUM), in collaboration with the Royal Technical University (KTH) in Stockholm, have developed stable nano-packaging for medicines. Through a special mechanism, the active ingredients should only be released in the diseased cells.

Our body is made up of billions of cells. In cancer, the genome of some of these cells is pathologically altered so that they divide in an uncontrolled manner. Even with virus infections, the cause of the disease is in the affected cells. During chemotherapy, for example, drugs are used to try to destroy these cells. However, the therapy affects the entire body, healthy cells are also damaged, and there are sometimes severe side effects.

A research team led by Prof. Oliver Lieleg, holder of the professorship for biomechanics and member of the Munich School of BioEngineering at TUM, and Prof. Thomas Crouzier from KTH have developed a transport system through which the active ingredient should only be released within the affected cells . “The active ingredient carriers are indeed absorbed by all cells,” explains Lieleg. “But only the diseased cells should have the ability to release the active ingredient.”

Synthetic DNA keeps the active ingredient carriers closed

The scientists have now been able to show that the mechanism works in tumor model systems from cell cultures. First, they packed the active ingredients. For this they use the so-called mucins. These are the main components of the mucus that is formed on the mucous membranes in the mouth, stomach or intestines, for example. Mucins are made up of a protein backbone to which sugar molecules are attached. “Since mucins occur in the body, opened mucin particles can later be broken down by the cells,” says Lieleg.

Another important component of the packaging can also be found in the body: deoxyribonucleic acid (DNA), the carrier of our genetic information. The researchers synthesized DNA structures with the properties they wanted and attached them chemically to the mucins. If glycerin is added to the solution in which the mucin DNA molecules and the active ingredient are located, the solubility of the mucins decreases, they fold together and enclose the active ingredient. The DNA strands bind together and stabilize the structure so that it can no longer unfold by itself.

The lock to the key

Only the right “key” can open the DNA-stabilized particles again, so that the encapsulated drug molecules are also released. The researchers use so-called microRNA molecules. RNA or ribonucleic acid is very similar in structure to DNA and plays a major role in protein synthesis in the body, but can also regulate other cell processes.

“In cancer cells, microRNA strands are present, the structure of which we know exactly,” explains Ceren Kimna, first author of the study. “In order to use it as a key, we have adapted the lock accordingly – by carefully designing the synthetic DNA strands that stabilize our drug carrier particles.” The DNA strands are structured in such a way that the microRNA molecules can bind to them and thus the existing ones Dissolve bonds that stabilize the structure. The synthetic DNA strands in the particles can also be adapted to microRNA structures that occur in other diseases such as diabetes or hepatitis.

The clinical application of the new mechanism has not yet been tested; beforehand, further investigations in the laboratory with more complex tumor model systems are required. The researchers also want to investigate further modifications to this mechanism for drug release in order to improve existing cancer therapies.

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