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New nanoparticles shrink tumors in mice
Date:8/15/2012

goal was to create a "mix and dose" technique that would allow researchers to mix up RNA-delivery particles that target a particular gene, inject them into mice and see what happens.

Shrinking tumors

In their first effort, the researchers decided to focus on the ID4 protein because it is overexpressed in about a third of high-grade ovarian tumors (the most aggressive kind), but not in other cancer types. The gene, which codes for a transcription factor, appears to be involved in embryonic development: It gets shut down early in life, then somehow reactivates in ovarian tumors.

To target ID4, Bhatia and her students designed a new type of RNA-delivering nanoparticle. Their particles can both target and penetrate tumors, something that had never before been achieved with RNA interference.

On their surface, the particles are tagged with a short protein fragment that allows them to enter tumor cells. Those fragments are also drawn to a protein found on tumor cells, known as p32. This fragment and many similar ones were discovered by Erkki Ruoslahti, a professor at the Sanford-Burnham Medical Research Institute at the University of California at Santa Barbara, who is also an author of the new paper.

Within the nanoparticles, strands of RNA are mixed with a protein that further helps them along their journey: When the particles enter a cell, they are encapsulated in membranes known as endosomes. The protein-RNA mixture can cross the endosomal membrane, allowing the particles to get into the cell's main compartment and start breaking down mRNA.

In a study of mice with ovarian tumors, the researchers found that treatment with the RNAi nanoparticles eliminated most of the tumors.

The researchers are now using the particles to test other potential targets for ovarian cancer as well as other types of cancer, including pancreatic cancer. They are also looking into the possibility of developing the ID4-targeti
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Contact: Sarah McDonnell
s_mcd@mit.edu
617-253-8923
Massachusetts Institute of Technology
Source:Eurekalert

Page: 1 2 3 4

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