The nanolipogels (light blue) release IL-2 (green), which activates the body's own immune system (purple). The small blue dots are the drug that inhibits TGF-β. Photo: Nicolle Rager Fuller, NSF
Read aloud US researchers have successfully tested in animal experiments, a novel drug system that can target drugs to tumors. It is based on so-called nanolipo gels (NLGs) - small, drug-filled globules with a gelatinous surface, which pass through the bloodstream into the tumor tissue where they release their cargo. Yale University's Tarek Fahmy scientists charged these beads with two anticancer drugs, which are usually difficult to combine, and thereby increased the success of cancer therapy in the mouse model. The problem with the conventional administration of many medicines is that you can not control where exactly they end up: the drugs work everywhere in the body and are not focused on the cancer alone, which among other things can lead to unwanted side effects. In addition, it is usually not enough to fight against the degenerate cells only on one front. The fat-coated globules can provide a solution to both problems, the scientists say: they bring the drugs right where they are needed, and they make it possible to deliver multiple drugs at the same time. In the scientists' test, there were two that could hardly be more different: the molecules of one are water-soluble and large, while the other is water-repellent and relatively small. In such a combination, it is usually necessary to administer the drugs in a row, which is usually at the expense of their effectiveness.

The scientists have solved this challenge with their tiny globules - 1, 000 of them together would be as wide as a human hair. They have a core with tissue structure in which the drug molecules are separated from each other, and a soft, gel-like shell. This also gives the nanolipo gels their name. All materials of the NLG are, comparable to self-dissolving threads in surgery, so biodegradable and seem to be well tolerated. In the experiment with mice, no side effects were observed. However, whether the NLGs are actually safe and suitable for humans must be determined in further studies.

For the also problematic addressing of the drug packages, the researchers took advantage of a special feature of cancer tissue: The vascular system of a tumor is more disordered and more branched than the normal bloodstreams in the body. Although small enough to travel across the body, NLGs remain stuck in the labyrinth of narrow and intersecting cancer vessels. Thus, they accumulate in the blood vessels of the tumor, even if they were not injected there. After a few days, the outer skin of the beads dissolves and the drugs work directly where they are needed: in the middle of the heart of the tumor.

The drugs that the researchers delivered in this double pack have completely different areas of work: One is an inhibitor for the so-called transforming growth factor β, or TGF-β. It is a signaling molecule of the tumor that confuses the immune system and slows down the body's defenses. The second drug that helped the team with NLGs is the cytokine interleukin-2 (IL-2). This protein alerts the immune system and thus strengthens the body's defense. Thus, the active substance double pack prevents, on the one hand, the tumor from suppressing the immune system and, on the other hand, improves the effectiveness of body defense. display

The double-stroke method has already proven its worth, at least in the laboratory: The researchers gave their NLGs to mice that were suffering from one of the most vicious cancers, black skin cancer. The results showed impressive results, the team reports: In comparison to mice that did not receive any or only one of the two drugs, the animals developed smaller and fewer tumors. All animals treated with both drugs in the NLGs survived, and at forty percent the tumor completely receded. Tarek Fahmy and his colleagues now hope their system will soon benefit human patients. They are also sure that in addition to the two active ingredients tested, other medicines can also be transported in the NLGs.

Tarek Fahmy (Yale University) et al .: Nature Materials, doi: 10.1038 / nmat3355 © Sabine Short


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