 Within a minute the drugs, using the new nanoparticle delivery system, are already clustering at tumor sites. (Source: Case Western Reserve University)
New technology using gold nanoparticles attacks tumors faster, more aggressively
While developing
new cancer killers is an important priority, half the difficulty in winning
the battle against cancer is just getting
the drugs to the tumor itself. The concept of drug delivery is an
important one as current blood borne chemotherapy treatments take two or more
days to reach the tumor fully.
Lots of exotic
methods have been devised to cut drug delivery time, but one of the more
promising ones comes from a new breakthrough from researchers at Case Western
Reserve University. The researchers successfully tested a new delivery
system, which brought cancer
drugs to tumors in lab mice within a couple hours of their injection.
To accomplish this ultra-speedy delivery, researchers used gold nanoparticle
vectors to deliver photodynamic therapy (PDT) drugs, a class of drugs that burn
away cancer with light via wavelength energization, to tumors. Case
Western Reserve University graduate student Yu Cheng, one of the paper's
coauthors explains, "Gold nanoparticles are usually not used for the PDT
drug vector. However, gold is chemically inert and nontoxic."
PDT drugs, which are seeing increasing use due to their efficacy, are typically
difficult to use properly. In order to prevent the drugs from being
prematurely activated, the patient must stay in dim light for days until the
drugs reach the tumor. With the new method, the drugs become much more
useful, as the inconvenience is lessened to a mere couple of hours.
Paper co-author Clemens Burda, associate professor of chemistry and director of
the Center for Chemical Dynamics and Nanomaterials Research at Case Western
Reserve University states, "By shortening the waiting time from drug
injection to activation, PDT patients are much less inconvenienced and tend to
have a more normal lifestyle."
The new delivery device consists of a gold
nanoparticle (Au NP) at its core. Gold nanoparticles are selected due
to their low toxicity, versatile surface chemistry, large surface-to-volume
ratio, and variable size and shape. The nanoparticle is then coated in
fatty polyethylene glycol (PEG) ligands, which make it resemble a hairy
ball. The coated molecule does not react with proteins and is fat and
water soluble, making sure it reaches the tumor intact.
A photodynamic chemotherapy drug (Pc 4) is inserted between each of the PEG
ligands, coating the ball with cancer drugs. This particular drug was
developed by Case Western Reserve's Malcolm Kenney, professor of chemistry.
The combined nanoparticle gravitates towards tumors within hours, thanks to
much faster dispersion. When it reaches the site, scientists use focused
red light to excite the PDTs and fry the tumor.
A small 1/4-mL injection holds 100 million Au NPs each with 100 PDT drug
molecules hitching a ride. The researchers hope to adapt the coated Au NP
system to a broad variety of bloodstream drugs to speed treatment.
In test on mice, the drug was injected in the mice's tails and within in
minutes the drug was gravitating around tumors in the mice's bodies.
Human trials, following the successful mouse trials have not yet been
planned. The Food and Drug Administration (FDA) will have to approve the
combined particle. This may be coming soon, though as the components --
Au Nps, PEG ligands and Pc 4 -- are all FDA approved.
The researchers hope to focus their future efforts on modifying the PEG
"hair" ligands" for speed and specificity. Also, they hope
to optimize and minimize drug and material load for a finished treatment.
Professor Burda says the beauty of the technology is that such adaptations and
optimization can easily be made.
Says Professor Burda, "The system is very modular. We can change the
size and shape of the Au core NPs and we can change the functionality of the
PEG ligands. This should lead to optimization of the drug targeting and
therapy. If our research is successful, other researchers might adapt this drug
delivery system to other diseases and applications."
The team's findings are reported
in a paper in the current issue of the Journal of the American Chemical
Society.
The research was funded by the National Science Foundation, National Institute
of Health/National Cancer Institute and the Biomedical Research Technology
Transfer Center.
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