HIV Drug Goes for Gold

 
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PostPosted: Wed May 13, 2009 10:04 am    Post subject: HIV Drug Goes for Gold Reply with quote

Gold nanoparticles shown to enhance effectiveness of drugs

The metaphorical gold standard of medical treatment might one day turn out to be a literal gold treatment.

By hacking off the ends of a failed HIV drug and sticking the resulting molecules onto gold nanoparticles, scientists have stopped HIV from infecting lab-cultured white blood cells. It is the first time gold nanoparticles have shown potential in therapies for HIV.

The same technique could eventually be put to use in treatments for a variety of diseases, say researchers not associated with the new study.

In the early 1990's scientists tested a drug called TAK779, which successfully prevented HIV from binding to human white blood cells but caused such severe side effects that it was ruled out as a useful therapy.

The problem-causing component of the drug molecule appeared to be an ammonium salt on one end. Lopping off that salt prevents the side effects, but it also renders the drug useless against HIV. The resulting molecule simply won't bind to the virus tightly enough.

By attaching the drug (minus the ammonium salt) to gold nanoparticles, researchers hoped to improve the drug's binding power to HIV.

Since gold is chemically inert, reacting to virtually nothing, it is ideal not only for jewelry but also for use inside the body. The idea is to use the much larger gold nanoparticles to shepherd around and concentrate the smaller, weakly binding drug molecules.

"It's the same idea as Velcro," said T. Eric Ballard, a scientist at North Carolina State University and a co-author on the new study, which was recently published online in the Journal of the American Chemical Society . "One interaction is weak, but if you have a lot of weak interactions together they make one strong interaction."

It worked. The researchers tested several ratios of drug molecules to nanoparticles and found that when each nanoparticle was equipped, on average, with 12 drug molecules, the drug appeared to be as effective against HIV as the original version with the side effect-inducing ammonium salt.

So far, the researchers have only tested the TAK779/gold nanoparticle combination in cultured cells. But without the ammonium salt, the drug could be again considered as a potential therapy, though it would require extensive testing before it could be used on patients.

"We took a small molecule that isn't active on its own, conjugated it to the gold nanoparticle, and suddenly it's a very good inhibitor of HIV," said Ballard.

The next step, according to David Margolis, a study co-author at the University of North Carolina , is to try and fuse other drugs onto gold nanoparticles.

Their next effort will be to attach an antiviral drug and a glucose molecule to the nanoparticles and see if they can be transported across the blood-brain barrier, creating a virus-killing drug in the brain, something that hasn't been possible before.

"They could potentially use this technique for any small molecule" to fight diseases, said Kimberly Hamad-Schifferli as she read the study.

Hamad-Schifferli studies gold nanoparticles at the Massachusetts Institute of Technology but was not involved in the JACS article.

"You could take a drug that is not very effective, apply the same technique, and make it much more effective, potentially minimizing its toxic side effects," she said.


Sources
Eric Bland: http://dsc.discovery.com/news/2008/05/21/gold-nanoparticles.html
Paper: http://pubs.acs.org/doi/abs/10.1021/ja710321g?cookieSet=1&journalCode=jacsat
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