Nanoparticles act as bait to deliver 'suicide gene' into cancer cells

Nanoparticle delivery of a payload of toxin, straight to the tumour location, without damaging healthy cells, is as effective as chemotherapy at killing ovarian cancer in mice — but without the nasty side effects. This new method, pioneered at the Lankenau Institute for Medical Research, Pennsylvania, US, is expected to be tested in humans within 18-24 months according to a report in the journal Cancer Research.

'What we did was deliver DNA that basically tells cells to die. But it is only turned on in ovarian cells,' explained Dan Anderson of the Massachusetts Institute of Technology, who worked on the study. 'People have had interesting success with viruses, but viruses have been fraught with certain safety problems.'

The team's solution was to create an 'artificial virus' delivery system - a biodegradable polymer that can be absorbed by the body once it is inside the cell - which is used to deliver DNA encoding a diphtheria toxin into the cancer cells. Once inside the target cells, the diphtheria toxin genes produce a protein which kills off the cancer cell, leaving any surrounding healthy cells intact. These nanoparticles were injected into mice with primary or metastatic ovarian tumours and the tumour volume was measured before and after treatment.

Untreated (control) tumours increased in volume by a factor of 4.1 to 6, significantly more than the 2-fold increase exhibited by the treated tumours. In addition, four of the treated tumours did not grow at all whilst all control tumours increased in size. The nanoparticle therapy was administered to mice with three different types of ovarian cancer and it was found that it prolonged life span by nearly four weeks and suppressed tumour growth more effectively than in mice treated with the clinically relevant doses of cisplatin and paclitaxel (a standard combination chemotherapy for women with advanced ovarian cancer). 'We've found these things are at least as efficacious, but are safer,' Anderson said.

Early stage ovarian cancer can be treated with a combination of surgery followed by chemotherapy, but there are no effective treatments for advanced ovarian cancer that recurs after surgery and primary chemotherapy. This means the majority of treated early stage cancers will relapse. 'This report is definitely a reason to hope,' said Janet Sawicki, a professor at the Lankenau Institute for Medical Research, and lead researcher on the study. 'We now have a potential new therapy for the treatment of advanced ovarian cancer that has promise for targeting tumor cells and leaving healthy cells healthy.'