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y using a new technique that
disguises anticancer drugs as fats, researchers have managed to safely deliver
much higher doses of the drugs than usual to the site of cancer tumors in mouse
models.
A
new 'disguise' method could allow researchers to safely deliver much higher
anticancer drug doses to tumors.
"It's
like a Trojan horse," says Prof. Nathan Gianneschi, from Northwestern
University in Evanston, IL.
Prof.
Gianneschi is speaking of a new strategy that he and colleagues have recently
devised for delivering anticancer drugs to tumor sites.
Through
this new approach — which the researchers have tested in mice and which they
describe in a study paper that appears in the Journal of the American Chemical Society —
the team was able to deliver a much higher dose of a common chemotherapy drug to
attack cancer cells.
"[The
drug] looks like a nice little fatty acid, so the tumor's receptors see it and
invite it in," Prof. Gianneschi explains. "Then the drug starts
getting metabolized and kills the tumor cells," he continues.
Not
only does this new strategy seem to deliver a higher drug dose to the cancer
cells more effectively, it also appears to have lower toxicity — and thus fewer
side effects — compared with current methods of delivery.
Safe delivery of much higher drug dose
The
"Trojan horse" that Prof. Gianneschi and the team developed is a
long-chain fatty acid that can bind to drugs at both of its ends. Once it had
bound to the selected drug, the compound then "hides" inside human
serum albumin, the main protein present in blood plasma.
Human
serum albumin is able to carry different molecules, including fatty acids,
easily transporting them to different sites around the body.
"It's like the fatty acid has a
hand on both ends: One can grab onto the drug and one can grab onto proteins.
The idea is to disguise drugs as fats so that they get into cells and the body
is happy to transport them around."
Prof.
Nathan Gianneschi
Because
human serum albumin provides many types of cell nutrients, receptors on cells'
surfaces "pick up" this information and "swallow" these
various molecules.
Cancer
cells are even greedier than healthy cells, as they seek to grow and spread.
Thus, cancer cells absorb the nutrients in human serum albumin at a faster
rate.
When
the albumin also carries hidden anticancer drugs, the cancer cells mistakenly
swallow those, too, according to the researchers. But as soon as the cancer
cells process the nutrients and the hidden drug, they die.
In
the current study, the research team tested this approach in mouse models of
three types of cancer, namely bone cancer, pancreatic cancer, and colon cancer. The
investigators used an already approved, commonly used chemotherapy drug,
paclitaxel, which they attached to the specially created long-chain fatty acid.
The
researchers found that, in the mouse model, this type of delivery led to the
complete elimination of cancer tumors.
Moreover, the team observed that this system allowed
them to deliver a 20 times higher dose of paclitaxel, compared with two other
drug formulations that had been approved by the Food and Drug Administration
(FDA).
And
even though the dose was so much higher than usual, the researchers found that
the new delivery system was also 17 times safer than other formulations, with
fewer potential side effects.
"Commonly
used small-molecule drugs get into tumors — and other cells. They are toxic to
tumors but also to humans. Hence, in general, these drugs have horrible side
effects," noted Prof. Gianneschi.
"Our
goal is to increase the amount that gets into a tumor versus into other cells
and tissues. That allows us to dose at much higher quantities without side effects,
which kills the tumors faster," he explains.
The
new research offers hope for more effective and safer methods of delivering
anticancer drugs to tumors in human patients.
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