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Nanoparticle factories churn out proteins - could manufacturecancer drugs at tumor sites by grass lawn





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Nanoparticle factories churn out proteins - could manufacturecancer drugs at tumor sites by
Article Posted: 06/17/2013
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Nanoparticle factories churn out proteins - could manufacturecancer drugs at tumor sites


 
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Posted: May 11th, 2012 Nanoparticle factories churn out proteins - Could manufacturecancer drugs at tumor sites ( Nanowerk News ) Drugs made of protein have shown promise in treating cancer, butthey are difficult to deliver because the body usually breaks downproteins before they reach their destination. To get around thatobstacle, a team of researchers from the MIT arvard Center for Cancer Nanotechnology Excellence (MIT arvard CCNE) has developed a new type of nanoparticle thatcan synthesize proteins on demand. Once these "protein actory"particles reach their targets, the researchers can turn on proteinsynthesis by shining ultraviolet light on them. The particles, say the investigators, could be used to deliversmall proteins that kill cancer cells, and eventually largerproteins such as antibodies that trigger the immune system todestroy tumors.

This work represents the first proof of conceptthat it is possible to synthesize new compounds from inert startingmaterials inside the body. The MIT arvard CCNE team, led by RobertLanger and member Daniel Anderson, published the details of thissystem in the journal Nano Letters ( "Remotely Activated Protein-Producing Nanoparticles" ). The researchers came up with the idea for protein uildingparticles when trying to think of new ways to attack metastatictumors hose that spread from the original cancer site to otherparts of the body. Such metastases cause 90 percent of cancerdeaths.

They decided to mimic the protein anufacturing strategyfound in nature. Cells store their protein uilding instructions inDNA, which is then copied into messenger RNA (mRNA). That mRNAcarries protein blueprints to cell structures called ribosomes,which read the mRNA and translate it into amino acid sequences.Amino acids are strung together to form proteins. The researchers designed the new nanoparticles to self ssemblefrom a mixture that includes lipids hich form the particles' outershells lus a mixture of ribosomes, amino acids, and the enzymesneeded for protein synthesis. Also included in the mixture are DNAsequences for the desired proteins.

The DNA is trapped by achemical compound called DMNPE, which reversibly binds to it. Thiscompound releases the DNA when exposed to ultraviolet light, givingthe investigators the ability to turn on protein production attheir command. In this study, particles were programmed to produce either greenfluorescent protein (GFP) or luciferase, both of which are easilydetected. Tests in mice showed that the particles were successfullyprompted to produce protein when irradiated with UV light. Waiting until the particles reach their destination beforeactivating them could help prevent side effects from a particularlytoxic drug.

However, more testing must be done to demonstrate thatthe particles would reach their intended destination in humans, andthat they can be used to produce therapeutic proteins. Indeed, theMIT arvard CCNE team is now developing nanoparticles that cansynthesize potential cancer drugs. Some of these proteins are toxicto both cancerous and healthy cells, it may be possible using thissystem to turn on protein production only in the tumor, avoidingside effects in healthy cells. The team is also working on new ways to activate the nanoparticles.Possible approaches include production triggered by acidity levelor other biological conditions specific to certain body regions orcells.

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