The principle of suicide cancer gene therapy
Cancer researchers have been exploring gene therapy as an experimental treatment to fight the deadly disease despite the obstacles that have surfaced along the way. A cross-European research team has now gained a foothold in this area by developing a nanoparticle that transports antitumor genes selectively to cancer cells. The researchers are hopeful that human trials could begin in 2011. Their findings were recently published in the journal Cancer Research.
The lack of safe and efficient systemic gene delivery vectors has adversely affected the potential of gene therapy in the clinic, according to the researchers. In previous research, the team found that polypropyleneimine dendrimer nanoparticles have the capacity for tumour transfection - the process of introducing nucleic acids into cells by non-viral methods - in tumour-bearing mice.
With an eye on increasing safety, the researchers explored the colloidal stability of nanoparticles and monitored the exact biodistribution of gene transfer in the entire body of the live subject, they said.
'Gene therapy has a great potential to create safe and effective cancer treatments, but getting the genes into cancer cells remains one of the big challenges in this area,' explained co-author Dr Andreas Schatzlein from the University of London. '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.'
For this study, the team used polypropyleneimine dendrimers as carriers for the genes and noted this specific dendrimer forms stable complexes with DNA that only seemingly break when inside tumour cells.
'Our biophysical characterisation shows that dendrimers, when complexed with DNA, are capable of forming spontaneously in solution a supramolecular assembly that possesses all the features required to diffuse in experimental tumours through the enhanced permeability and retention effect,' the authors wrote.
Despite it being tested solely in mice, the researchers conveyed their optimism for getting human trials off the ground in two years' time. The technique could prove beneficial for patients suffering from unmanageable cancers because the healthy cells stay healthy.
Led by Dr Georges Vassaux of the National Institute of Health and Medical Research (INSERM) in France , the team showed that the cells are forced to generate proteins capable of killing the cancer when the genes are enclosed in the nanoparticles.
'Once inside the cell, the gene enclosed in the particle recognises the cancerous environment and switches on,' Dr Schatzlein said. 'The result is toxic, but only to the offending cells, leaving healthy tissue unaffected.'
According to the researchers, the cells produced the Na/I (sodium-iodide) symporter ( NIS ) which became visible in whole-body scans of the mice. While the transfected gene was expressed in cancer cells, it was not at an observable level in healthy cells, they added.
'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,' the researchers highlighted.
Other participants of this study included the Instituto Aragonés de Ciencias de la Salud in Spain , the University of Bordeaux in France and the London National Health Service Trust in the UK .
Source: CORDIS /...