Delivering cancer drugs inside gold-coated liposomes, an invention developed at the University of Arizona, could help chemotherapy treatments kill cancer cells more effectively without harming healthy cells and causing side effects.
The invention is the work of Dr Marek Romanowski, an associate professor of biomedical engineering in the University of Arizona (UA) College of Engineering in Tucson. He is also a member of the BIO5 Institute and the Arizona Cancer Center.
Graduate students Xenia Kachur and Sarah Leung are both working on the project in Romanowski’s lab.
They are trying to develop a way of making the gold-coated liposomes deliver cancer drugs in controlled doses without harming healthy body cells.
Liposomes are artificially created vesicles, tiny nano-scale capsules that transport materials inside cells.
When used in chemotherapy treatments they enclose the cancer drug in a skin made of organic lipids that are already present in human cells. This stops the immune system from attacking them before they can deliver the drug.
Liposomes work their way into cancer tumors because tumor blood vessels have “leaky vasculature”, that is extra openings through which they extract nutrients from the bloodstream (this helps them grow faster). As the growing tumor takes in nutrients it accumulates liposomes, which then break down, releasing the drug that kills the cancer cells.
However, cancer drugs are also highly toxic to healthy cells, and with no way to discriminate between healthy and cancer cells, healthy cells are also harmed, causing the side effects that patients experience when undergoing chemotherapy treatment with varying degrees of severity, such as anemia, vomiting, hair loss, and nausea.
Another problem is lack of control over how and when the liposomes release the enclosed drugs.
“There’s a particular concentration at which you have optimal results, so below that you don’t have enough of the drug to get a good response, and above that it might be even more toxic,” explained Leung.
The liposomes being developed in Romanowski’s lab address both these problems with two special features: they are coated in gold and they carry a ligand molecule that allows them to “dock” more easily onto cancer cells as opposed to healthy cells.
Gold converts near-infrared light into heat. Romanowski’s team are working on a way to exploit this property, as Kachur explained:
“The gold converts the light into heat, the heat causes the liposome to become leaky, and then whatever’s really concentrated inside can diffuse out through the leaky liposome.”
Infrared light penetrates deep into the body without causing a lot of heat because it interacts minimally with most tissues.
The idea as to control the amount of drug released from the gold-coated liposomes by varying the intensity of infrared light the patient is exposed to.
“By using more or less light, you can release more or less of the drug and time the responses as well, so when you trigger light, some drug will leak, you can trigger it again and have more drug leak, or you can wait a little while, let the drug disperse, do its thing, then trigger it again,” said Leung.
“It allows for a lot more freedom with the release process. By having this very triggered response you can hit that therapeutic window,” she added.
The other feature Romanowski’s lab researchers are working on is to attach specific ligands to the liposomes, depending on which cancer the drug is targeting. Different types of cancer cell over-express certain receptors, for various reasons.
A ligand is a molecule that allows whatever it is attached to to “dock” onto a target cell with a matching receptor. The receptor is like a lock, and the ligand is the key, in the same way that each lock has its own key, each receptor has its own ligand.
“It all depends on the disease that we’re targeting, but in the case of tumor cells, they over-express certain receptors for several reasons.”
“One is tumor cells are proliferating very quickly, and so they’re over-expressing a lot of nutrient receptors because they want to divide faster,” she explained.
Because the cancer cells are over-expressing these receptors, by carrying the matching ligand, the liposomes are then more likely to attach to the cancer cells than to the healthy cells.
Another possible benefit of the gold coating is that it could stop liposomes that do end up in healthy cells from releasing the cancer drugs.
As Leung explained, by shining the infrared light only in the tumor region, doctors could make sure only the liposomes that end up in the tumors release the drug:
“Once you know where the tumors are, you can go ahead and point your light source toward those areas,” she said.
“Whatever else is left will leave the body or may be slowly released, but not to as high or as toxic a level as it would be if you just injected the drug systemically,” she added.
Another advantage of the gold coating is that it is bio-degradable.
“Because of the size it degrades into, our system should be clearable via the kidney, which is really unique,” said Leung.
There is still a long way to go before Romanowski’s liposomes are ready for use in cancer therapy. But if it passes all the tests, the researchers hope the new invention will help drugs target cancer cells more easily, non-invasively trigger drug release via infrared light, and provide a way for the body naturally to eliminate the drug from the bloodstream.
The researchers are hopeful their work will one day mean cancer patients can have confidence their chemotherapy treatments will be effective without fear of suffering any harmful side effects.
Grants from the National Institutes of Health and the National Science Foundation are helping to pay for the research.
Source: UA News.
Written by: Catharine Paddock, PhD