Bacterial protein treats cancer by releasing drugs from liposome carriers.
US scientists have given a new meaning to the term ’friendly bacteria’ by discovering a bacterial protein that helps treat cancer. The bacteria that produce this protein prompt drug-laden liposomes to release their load when they reach the tumour target.
Sealing powerful cancer drugs inside liposomes - water-filled lipid casules - can protect healthy cells from the indiscriminate collateral damage caused by chemotherapy. Using this method, a group of researchers from Johns Hopkins University in Baltimore discovered that liposomes could be opened up, or lysed, at the exact site where their drug cargo is needed, by bacteria that selectively infect tumour cells. The system was tested on mice, using the tumour-specific bacteria Clostridium novyi-NT (C. novyi-NT).
The team used mice with large, established colorectal tumours. When the mice were injected with liposome-encapsulated doxorubicin, a powerful DNA-damaging cancer drug, along with the bacterial spores, tumours were largely eradicated.
All of the mice treated directly with the free, unencapsulated drug died within two weeks, highlighting problems caused by the vicious toxicity of some chemotherapeutic agents.
The researchers explained that C. novyi-NT are anaerobic and thrive in the hypoxic conditions within tumours, where blood vessels are underdeveloped and sparsely distributed. These blood vessels are also very perforated and permeable, so liposomes can leak through their walls and into the tumour cells. Once there, they stay to release their dose of cancer-fighting drug.
Team member Ian Cheong told Chemistry World that the idea to use C. novyi-NT came from the group’s previous observations that the bacteria secrete a protein that can lyse and release haemoglobin from red blood cells. ’We thought that we could use this property to release drugs from liposomes within tumors colonized by the bacteria,’ he said.
In the second part of their study, the group wanted to identify what factor was breaking into the liposomes. ’We were astounded to discover that the agent primarily responsible for drug release from liposomes was not a hemolytic protein as originally thought, but a new lipase which we dubbed liposomase,’ Cheong explained.
Leaf Huang from the University of North Carolina, US, told Chemistry World that this study could be a starting point for a new clinical investigation. ’This is very exciting work,’ he said. ’There is still an enormous amount of work to be done - I think there will have to be a lot more safety testing of these bacterial spores before they can be injected into humans, but I think that gene therapy would be a very promising way to go. Making tumours express this protein could be the basis for a clinical investigation.’
Cheong admits that any bacterial infection, even one constrained to tumours can cause problems such as inflammation and even sepsis, but having used the bacteria safely in rodents and rabbits, he hopes to apply the research to human patients.
Patients are already being enrolled for a Phase I clinical study at the Johns Hopkins Hospital.
et alScience, 2006, 314, 1308
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