Scientists from Cancer Research UK have developed a new treatment that they successfully tested on mice whereby tiny nano particles carried anti-tumor genes into cancer cells and “zapped” them by causing them to make proteins that killed the cancer.

The research was done by Cancer Research UK’s Dr Andreas Schatzlein, who is based at the School of Pharmacy in London, and colleagues, and was published online on 10 March in the journal Cancer Research.

Previous studies have shown that this type of gene therapy can shrink tumors, and even cure about 80 per cent of the mice, and the hope is that treatments based on this method can save lives by helping people with inoperable tumors, such as those that are close to vital organs like the brain or lungs.

Gene therapy doesn’t kill cells indiscriminately, unlike chemotherapy, which is more of a scattergun approach that kills all cells in the affected area, including healthy ones. This is why chemo patients often have side effects like fatigue, hair loss and nausea. By targeting cancer cells only, the hope is that gene therapy won’t have such side effects.

The missing link supplied by this study is that the researchers found not only a way to get anti-tumor genes into nanoparticles and remain stable, but they also found a way to make them seek and target only the cancer cells and leave healthy cells untouched. This means the method could potentially be developed to treat cancer that has spread.

As Schatzlein explained:

“We hope this therapy will be used to treat cancer patients in clinical trials in a couple of years.”

” This is the first time that nanoparticles have been shown to target tumours in such a selective way, and this is an exciting step forward in the field,” he added.

Once inside the cell, the genes inside the particle switch on in response to the cancerous environment, and start issuing instructions to make proteins that are only toxic to the cancer cells, leaving healthy cells unaffected, explained Schatzlein.

For the study, Schatzlein and colleagues were able to produce “colloidally stable” nanoparticles ranging from 33 to 286 nm that were capable of carrying evenly distrubuted DNA molecules and diffusing in experimental tumors in live mice.

They deployed “whole-body nuclear imaging using small-animal nano-single-photon emission computed tomography/computer tomography scanner and the human Na/I symporter (NIS) as reporter gene” to show that the nanoparticles had targeted and entered only the cancer cells and none of the genes had transferred to any of the healthy tissue of the tumor-bearing mice.

They also performed post-mortem tests on the mice to confirm that the nanoparticles had accumulated at tumor sites and that “tumor-selective transgene expression” had taken place.

The researchers concluded that:

“Considering that NIS imaging of transgene expression has been recently validated in humans, our data highlight the potential of these nanoparticles as a new formulation for cancer gene therapy.”

Director of cancer information for Cancer Research UK, Dr Lesley Walker who has a PhD in immunology and is an experienced research scientist herself, said in a press statement that these results were encouraging and they were looking forward to seeing if the approach developed by Schatzlein and colleagues will work in humans.

“Gene therapy is an exciting area of research, but targeting genetic changes to cancer cells has been a major challenge, said Walker.

“This is the first time a solution has been proposed, so it’s exciting news,” she added.

“Cancer-Specific Transgene Expression Mediated by Systemic Injection of Nanoparticles.”
Edward J. Chisholm, Georges Vassaux, Pilar Martin-Duque, Raphael Chevre, Olivier Lambert, Bruno Pitard, Andrew Merron, Mark Weeks, Jerome Burnet, Inge Peerlinck, Ming-Shen Dai, Ghassan Alusi, Stephen J. Mather, Katherine Bolton, Ijeoma F. Uchegbu, Andreas G. Schatzlein, and Patrick Baril.
Cancer Research first published on March 3, 2009.

Click here for Abstract.

Sources: Journal article, Cancer Research UK.

Written by: Catharine Paddock, PhD