04 December 2017

Nanoparticles against cancer stem cells

Researchers from the University of Illinois have developed nanoparticles capable of finding and attaching to the CD44 protein, which is found only on the surface of virtually elusive cancer stem cells, and tested them in cell culture and on mice with breast cancer.

If a nanoparticle carries a drug that disables certain genes in cancer stem cells, then it is possible to deprive the latter of "stemness", that is, the ability to divide and turn into tumor cells. For this purpose, the drug niclosamide was chosen, which is currently used to treat parasitic diseases, but can also interfere with the regulation of the gene activity of the cell.

Cancer stem cells are cells with the properties of "classic" stem cells. They are able to divide and differentiate into tumor cells even after a long period of inactivation. This allows them to make possible the recurrence of the tumor long after a successful course of treatment.

Since the discovery, researchers' interest in cancer stem cells as a potential target for anticancer drugs has been growing day by day. In order to achieve a complete cure of the patient, it is necessary to find these rare cells and destroy them. Nanotechnology can be a useful tool, because nanoparticles work on the same scale as almost all biological processes.

There is a set of STAT genes (signal transducer and activator of transcription, signal receiver and transcription activator) encoding proteins that are capable of penetrating into the cell nucleus when receiving certain signals. There they connect to DNA and switch other genes to the "on" or "off" state.

STAT3 genes are a type of STAT that play a role in many cellular processes, including growth, division, movement and apoptosis (self–destruction) of cells. STAT3 of tumor cells seemed to researchers to be the optimal target for new drugs.

In a study in cell culture and in live mice, it was shown that nanoparticles with niclosamide, binding to the CD44 membrane protein of a breast tumor cancer stem cell, turned off STAT3. Stem cells lost their ability to divide and differentiate, which greatly reduced the likelihood of recurrence and metastasis of the tumor.

STAT3.jpg

Nanoparticles (black) are able to target cancer stem cells (yellow) and supply them with a drug that inhibits their growth. A drawing from the University Of Illinois Urbana-Champaign Drug-delivering nanoparticles seek and destroy elusive cancer stem cells press release.

In addition, the rate of tumor growth decreased in mice and in the background of the introduction of nanoparticles in cell culture.

The authors hope that the results of their research will help further work on new drugs for the treatment of cancer and the prevention of relapses and metastases. They name the relatively low cost of treatment as the advantages of the method described by them, because the drug niclosamide has already been approved and does not have to go through all phases of clinical trials. It is included in the WHO main list and is recognized as a safe and effective drug. The manufacture of nanoparticles should also not greatly affect the price, since they are a polymer that can be produced in large quantities.

In addition, the results of the study will be of interest to those who study cancer stem cells: in it, the authors described the proteins and genes responsible for the vital processes of cancer stem cells.

Currently, it is planned to conduct research on larger animals in order to bring nanoparticles with niclosamide one step closer to use in clinical practice.

Article by Santosh K Misra et al. Targeted Delivery of STAT-3 Modulator to Breast Cancer Stem Like Cells Down-regulates a Series of Stem-ness Genes published in the journal Molecular Cancer Therapeutics.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru according to Medical News Today: Cancer stem cells destroyed by drug-filled nanoparticles


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