Potential Cure For Ovarian Cancer Using Nanoparticles
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Potential Cure For Ovarian Cancer Using Nanoparticles
While following cancer-cell genomes, a high number of mutated, deleted or copied genes were discovered. This medical breakthrough gives researchers the possibility of finding new drug targets, but it’s almost impossible to have them all tested in a short period of time.
RNA-delivering nanoparticles were developed by MIT researchers in oder to give the possibility of a faster way to screen new drug targets in mice. Researchers from Dana-Farber Cancer Institute and Broad Institute showed that these nanoparticles target an ID4 protein and this way shrink ovarian tumors.
“What we did was trying to set forth a pipeline where you start with all of the targets that are pouring out of genomics, and you sequentially filter them through a mouse model to figure out which ones are important. By doing that, you can prioritize the ones you want to target clinically using RNA interference, or develop drugs against,” said professor Sangeeta Bhatia.
There are many potential targets for cancer drug treatments, but there is also a high number of targets that can not be drugged. This means that the proteins don’t have any receptors where a traditional drug could bind to them. The main part of nanoparticles is that by delivering small amounts of RNA that can shut off a particular gene, they might help making those proteins that can not be drugged more accessible.
“If we could figure out how to make this work [in humans], it would open up a whole new class of targets that hadn’t been available”, said professor William Hahn from the Harvard Medical School. William Hahn is also the leader of Project Achilles, focused on identifying new possible targets for cancer drugs.
Thanks to Project Achilles, Hahn’s team were able to test the functions of numerous disrupted genes in ovarian cancer cells, which considerably reduced the potential targets list. Moreover to identify a good drug target the scientists had to turn off the responsible genes after the tumor appears.
A fast and efficient way to turn off these genes is through RNA interference. During this process, short strand of RNA bind to the messenger RNA, that delivers instructions on how to build proteins from the cell’s nucleus to the rest of the cell. After bounding, the mRNA molecules are destroyed and this way, proteins never get made.
The researchers’ main purpose is to create a “mix and dose” technique which would give the researchers the possibility to mix up RNA-delivery particles that target a particular gene, then inject them into mice. They have chosen to focus on ID4 proteins because of its over expression in almost a third of high-grade ovarian tumors. The gene is involved in embryonic growth which means it gets shut down early in life and reactivated later in ovarian tumors.
A new type of RNA-delivering nanoparticles was created in order to target the ID4. This nanoparticles can target and penetrate tumors for the first time. Bhatia’s team created the particles with a small protein fragment on their surface, which allows them to penetrate tumor cells. The particles’ protein fragments are drawn p32 proteins found on tumor cells.
Inside the nanoparticles there are strands of RNA mixed with proteins that help them survive until they are encapsulated in the cells’ membranes as endosomes. Thanks to this RNA-protein mixture, nanoparticles can travel through the endosomal membrane, enter the cell’s main compartment and start breaking down mRNA.
During their study, researchers discovered that the treatment with RNAi nanoparticles eliminated most of the mice ovarian tumors. Furthermore they are currently using the nanoparticles for potential targets in other types of cancer. They are also considering the possibility of developing the particles as a new, effective treatment for ovarian cancer.