Nanotechnology weapons for cancer

By Dr. Ananya Mandal, MDMar 22 2010

US Researchers have come up with new nanoparticle robots that are essentially a tiny army that can travel in the blood till they reach the cancers and then tweak some important cancer causing genes that can cure the cancer.

These findings were reported in a Journal called Nature on Sunday. This new tool can attack vulnerable areas of a protein that are hidden within its three-dimensional folds, making it difficult for doctors to reach them. RNA interference targets the messenger RNA, or mRNA, that encodes the information that confuses regular cells and makes them cancerous.

Many biotechnology and pharmaceutical companies including Alnylam, Merck, Pfizer, Novartis and Roche are looking for ways to manipulate RNA to block genes that make disease-causing proteins involved in cancer, Pakinsonism, chronic pain, blindness or AIDS.

The finding

This is a finding of a team at the Calfornia Institute of Technology in Pasadena. They have been tinkering with nanotechnology that deals with really small particles quite invisible to naked eyes. These particles are made into tiny robots that have a protein jacket called Transferrin. These particles search for a receptor that is a molecular door in the cancerous cell.

"This is the first study to be able to go in there and show it's doing its mechanism of action," said Mark Davis, a professor of chemical engineering, who led the study.

Davis said, "RNAi is a new way to stop the production of proteins."

"We're excited about it because there is a lot of skepticism whenever any new technology comes in," said Davis, a consultant to privately held Calando Pharmaceuticals Inc, which is developing the therapy.

Apart from nanoparticles fat particles have also been utilized for this purpose. Pfizer last week announced a deal with Canadian biotech Tekmira Pharmaceuticals Corp for this type of delivery vehicle for its RNAi drugs, joining Roche and Alnylam.

In this experiment by Davis and colleagues, the nanoparticles find the cancer cell and then get inside. Once they break down the RNA, they form siRNA or Small Interfering RNA. These siRNAs block a protein called ribonucleotide reductase that is a key in cancer growth.

"In the particle itself, we've built what we call a chemical sensor," Davis said in a telephone interview. "When it recognizes that it's gone inside the cell, it says OK, now it's time to disassemble and give off the RNA."

"There are many cancer targets that can be efficiently blocked in the laboratory using siRNA, but blocking them in the clinic has been elusive," said UCLA associate professor of medicine Antoni Ribas. "This is because many of these targets are not amenable to be blocked by traditionally designed anti-cancer drugs. This (new) research provides the first evidence that what works in the lab could help patients in the future by the specific delivery of siRNA using targeted nanoparticles," Ribas said. "We can start thinking about targeting the untargetable."

Does it work in Humans?

In its initial phase of trial in humans (Phase 1 Clinical trial) these nanoparticles were administered four times over 21 days in a 30-minute intravenous infusion. Tumor samples taken from three people with melanoma showed the nanoparticles found their way inside tumor cells. And they found evidence that the therapy had disabled ribonucleotide reductase, suggesting the RNA had done its job.

Davis did not claim that this therapy will shrink the tumors but one of the patients was given a second cycle. This was suggestive that this therapy might be working. He did not raise any safety concerns with this therapy.

Davis said that part of the study will be presented at the American Society of Clinical Oncology meeting in June.