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14/11/2019

Managing Zileuton by means of polymeric micelles significantly reduces the tumor stem cells of breast cancer within the tumor and in the bloodstream

zileuton_884

14/11/2019

Zileuton administered in polymer micelles better reaches the inside of the tumor reducing the amount of CSC within the tumor as well as circulating tumor cells.

The http://en.vhir.org/portal1/grup-equip.asp?s=recerca&contentid=186781 CIBBIM-Nanomedicine. Drug Delivery and Targeting Group of the Vall d'Hebron Research Institute (VHIR) has conducted a study to measure the effectiveness of Zileuton &trade,, a drug that is indicated for the treatment of asthma, administered through micelles. The polymeric against tumor stem cells in triple negative breast cancer, one of the most aggressive tumors. The study was published in the journal https://www.sciencedirect.com/science/article/abs/pii/S154996341930190X?via%3Dihub#f0005 Nanomedicine: Nanotechnology, Biology and Medicine and was attended by the CIBBIM-Nanomedicine. Biomedical Research in Digestive Tract Tumors research group and the Area of Functional Validation & Preclinical Research of the CIBBIM- Nanomedicine of the VHIR.Tumor recurrence and metastatic dissemination in advanced cancers are supported by the presence of cancerous stem cells (CSCs) in the tumor and in the circulatory torrent. Often, the use and efficacy of new therapies against cancer are hampered by CSC resistance to chemotherapeutic treatments and underlying pharmacokinetic and pharmacodynamic conditions of the drugs used. Therefore, the administration of drugs through nanotransporters has great potential to increase efficacy and reduce toxicity and adverse effects.The team of researchers led by Dr. Simó Schwartz Jr. it has developed polymeric micelles to transport Zileuton &trade,, a potent inhibitor of the ALOX5 gene. This gene is involved in the maintenance and survival of CSCs in leukemia and also in triple negative breast cancer, as described by the research group in this work. First, the researchers confirmed that CSCs of these tumors overexpress ALOX5 in 86% of cases, and validated this target for the treatment of breast cancer.The great potential of this inhibitor to eliminate CSC was subsequently demonstrated in in vitro and in vivo CSC fluorescents models, also developed by Dr Schwartz Jr. In this way the researchers conclude in the study that " transport Zileuton &trade, with polymeric micelles allows the drug to reach better inside the tumor effectively reducing the amount of CSC in the tumor as well as the cells, Tumor cells circulating in the bloodstream, responsible for metastatic dissemination", says Dr. Schwartz Jr.The advantage of using micelles as drug nanotransporators is that they facilitate their solubilization, and therefore, they can be administered intravenously in a more effective way, increasing the amount of drug that reaches the tumor. They also make it easier for the tumor cells to incorporate the drugs inside them. The micelles designed in the study are stable, have no toxicity (even at high doses), and are easily eliminated by the body. On the other hand, it should be mentioned that although these micelles are not actively directed to the tumor by any mechanism, in animal models the researchers have been able to verify how the micelles loaded with the drug accumulate sufficiently in breast tumorsWhen working on animal models, by injecting the micelles loaded with Zileuton &trade, directly into the bloodstream, it was observed that not only the number of CSCs of the tumors was significantly reduced, but also that these disappear completely from the torrent blood vessels. "Zileuton &trade,, although it does not have an antiproliferative effect on tumors, could be a good candidate as an antimetastatic agent, especially in combination with other chemotherapeutics," concludes Dr. Schwartz Jr.

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