By Roland Piquepaille
Today, anticancer drugs are delivered to patients in such a way that they can destroy both infected and healthy cells. But now, researchers at the Institute of Bioengineering and Nanotechnology (IBN), in Singapore, have designed 'smart' nanocarriers which deliver the drugs exactly where they are needed, reducing side effects and suppressing cancer growth. Their core-shell nanoparticles are both sensitive to temperature -- which has been done before -- and to acidic levels. When these nanocarriers encounter acidic environments such as tumor tissues, they break apart and release the molecules they contain. So far, this technology has only been tested on mice, but the researchers have filed an application patent in the U.S., so expect to see practical applications in a few years. Read more...Before going further, please note that this IBN news release, published by PhysOrg.com on April 26, 2005, was originally issued by IBN on March 21, 2005. You can find the original version here (PDF format, 2 pages, 49 KB).
So what's the situation of anticancer drugs delivery today?
Anticancer drugs are now being administered to patients using methods that cause the indiscriminate killing of both diseased and healthy cells. [...] Hence, there is a crucial need for the development of more effective cancer therapy, which not only minimizes side-effects but also directly targets diseased cells.
Scientists at IBN have found a way to tackle this problem through the use of anticancer drug delivery vehicles that transport drugs only to where they are needed in the body. This method significantly reduces or even eliminates the severe side-effects typically induced by conventional chemotherapeutics.
So what exactly is this new method?
The team led by IBN Group Leader Dr Yi-Yan Yang has created 'smart' nanocarriers that can house anticancer drugs in their inner cores. Such polymeric core-shell nanoparticles are small in size (generally less than 200 nm), with shells that protect enclosed bioactive compounds against degradation and digestive fluids.
These nanocarriers, which are both pH-sensitive and temperature-sensitive, are structurally stable in the normal physiological environment. However, in slightly acidic environments that are characteristic of tumor tissues and endosomes (a cell component), they deform and precipitate, thus releasing the enclosed drug molecules.
The key idea behind this new technology is obviously that these nanocarriers are pH-sensitive.
"Previous attempts by other scientists involved the use of core-shell nanoparticles that were only sensitive to temperature. Drug delivery may be controlled by superficially heating and cooling the environment of the nanoparticles," said lead scientist Dr Yang.
"The novelty of our invention compared to carriers that are only temperature-sensitive is the ability of IBN's core-shell nanoparticles to target drugs to deep tissues or cell compartments without changes in temperature."
Now, two questions need to be answered: is this technology efficient? and does it suppress side effects?
So far, the IBN team has proven that their core-shell nanoparticles can deliver anticancer drugs much more efficiently into cancer cells, compared to current techniques. Their in vivo studies using a mouse breast tumor model has also shown that doxorubicin (an anti-cancer drug) loaded in these smart nanoparticles can suppress tumor growth more efficiently than free doxorubicin.
"IBN's 'smart' nanocarriers do not show significant cytotoxicity, and offer great potential in targeting drugs to tumor tissues with high efficacy," added Dr Yang. "This invention may also be used in in vitro and animal studies for drug discovery."
The research work has been published online by Advanced Materials on February 4, 2005(Volume 17, Issue 3, Pages 318-323) under the title "pH-Triggered Thermally Responsive Polymer Core-Shell Nanoparticles for Drug Delivery." Unfortunately, this link to the paper doesn't provide an abstract.
But you'll find few more details on this page at IBN about "Stimuli-Sensitive Core-Shell Nanoparticles for Cancer Therapy." [Please note that the URL of this page has been built manually: it's not directly available from the IBN site.]
Conventional chemotherapies for cancer treatment have significant toxic side-effects due to the non-specific absorption of anticancer drugs by all cells. The aim of our project is to develop a smart and safe delivery system to target drugs specifically to tumor cells.
In this project, novel core-shell polymer nanoparticles are designed with their lower critical solution temperature (LCST) being dependent on the ambient pH. This value is above the nominal physiological temperature of 37°C at pH 7.4, but decreases to a temperature below the physiological temperature with a small decrease in pH. The resulting change in LCST causes the core-shell nanoparticles to deform and precipitate in an acidic environment, triggering the release the chemotherapeutics at low pH. In addition, a biological signal has been conjugated to the shell of the nanoparticles, which can recognize tumor cells. This system may be able to target drugs to tumor cells and release the drugs intracellularly.
Finally, the researchers filed a patent application in the U.S. under the name "Nanostructured thermosensitive membranes as wound dressing."
I can't give you more details today as the search engine of the United States Patent and Trademark Office (USPTO) seems to be broken, returning internal errors. But try another day: with the name, it should be pretty easy to find it in the USPTO database.
Sources: Institute of Bioengineering and Nanotechnology, March 31, 2005; and various websites
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