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Forbes salute nanoparticle chemotherapy

By Mike Nagle , 05-Jan-2007

Forbes has highlighted the important role of nanotechnology in driving forward the pharmaceutical industry with three of their top five nanotech breakthroughs in 2006 having biological applications.

Scientists at the Massachusetts Institute of Technology (MIT) and Harvard have designed nanoparticles that target cancer cells to deliver a localised dose of chemotherapy drugs.

 

Anti-cancer drugs are by nature designed to kill cells. However, many are not selective enough to recognise which cells are normal and which form part of a tumour. This leads to many of the side effects associated with chemotherapy.

 

Speaking to Drugresearcher.com, Dr Omid Farokhzad from Harvard University, US, said: "Our targeted nanoparticles are designed and engineered to differentiate tumour cells from normal cells and once inside the cancer cell, to release their chemotherapy payload.

 

"We are able to get a substantially higher dose inside the cancer cell but actually using a much lower overall dose."

 

The result is that not only are more cancer cells destroyed but also fewer healthy cells are killed, leading to fewer side effects.

 

"With a normal cancer drug, dosing is limited by toxicity but with targeted nanoparticles that reduce these adverse effects, it is possible to increase efficacy while decreasing toxicity," said Dr Farokhzad.

 

The type of nanoparticles designed by Dr Farokhzad and his colleague Robert Langer from MIT, called aptamers, are small strips of RNA that can form a huge variety of structures and so bind to many different targets. However, by choosing the right nucleotide sequence, you can design an aptamer with a specific structure that will only bind to one target.

 

In this case, the scientists developed an aptamer that recognises and binds to a specific antigen found on the surface of cancer cells in prostrate cancer.

 

The scientists then compared aptamer-delivered chemotherapy to traditional chemotherapy in mice that had been given human prostate cancer. Five of the seven mice had complete tumour reduction using aptamer delivered chemotherapy compared with only two that received traditional treatment.

 

Also, using their new technology, survival rates were 100 per cent over the study period, compared to only 57 per cent using traditional chemotherapy.

 

"Amazingly, a single administration of the drug was enough to achieve tumour eradication," said Dr Farokhzad.

 

Although nanoparticle delivery systems do lead to more expensive drug treatments, Dr Farokhzad explained: "When you look at overall healthcare costs, there is expected to be a substantial saving."

 

Having already demonstrated the efficacy of the system in mice, the team hopes to move into human trials within the next two years.

 

Dr Farokhzad said: "We have put together a system where we believe there's a very high chance of clinical success."

 

The team have achieved this by using components that have already been approved by the FDA and ensuring the process is both easy to manufacture and easy to scale up.

 

The technology is now being investigated for use in a range of other diseases such as pancreatic and breast cancer and cardiovascular disease. In addition, Dr Farokhzad said the research team are also looking into much more sophisticated, multi-functional systems.

 

Such nanoparticles systems could, for example, sense, image and treat cancer at the same time or sutomatically stop dosing a drug when necessary.

 

Paul Rothermund from California Institute of Technology (Caltech), US, was also given an award for his development of 'DNA origami'. Rothermund invented a technique to arrange a single strand of DNA into any 2D shape using shorter strands of DNA to hold it in place.

 

The resultant DNA scaffold could be used, for example, to hold proteins in the specific way they are arranged in live cells but also allowing scientists to work independently of living materials, giving them much more freedom in their research.

 

A further award was given to another research team from Harvard led by Charles Leiber. They developed silicon nanowires that link to live mammalian neurons, allowing them to model complex brain activity.

 

Although not one of the top five, a third Harvard research team were also recognised by the awards. The scientists, led by Robert Westervelt created a chip that can control the motion of biological cells, enabling cells to be assembled one by one into artificial tissue. This can then be used to test drug efficacy.