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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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