Cancer-Fighting "Molecular Velcro"
I'm getting off to a bit of a late blogging start today, thanks to the lack of readily available wireless service in the Moscone Center. Even my hotel only has wireless on the second floor meeting room area. I'm currently blogging from a nearby Starbucks, which at least is offering free samples of its new gingerbread latte. (A gratuitous bit of advice for all hotels and convention centers: wireless is no longer an optional service; for many of us, it's an absolute necessity. It's amost 2007, so get with the technological program already, or get left behind! Not that I'm bitter....)
It makes it even more difficult to find time to blog in between back-to-back scheduled sessions, which is too bad because the very first session this morning was chock-full of interesting talks. I'll just mention one of them here: the development of nanoscale dendrimers for targeted drug delivery to kill cancer cells. James Baker of the University of Michigan's Nanotech Institute for Medicine and Biological Sciences was on hand to describe his research group's proof-of-principle success in creating what he calls "molecular velcro": synthetic nanoparticles called dendrimers (or dendritic polymers) that are built up spherically layer by layer. They have proven highly effective as a targeted drug delivery mechanism to fight certain types of cancers.
Some folks might remember hearing about this breakthrough early last year. Baker and his colleagues essentially created a kind of "Trojan horse" that tricks cancer cells into absorbing the lethal (to the cancer cell, anyway) drug. Specifically, it exploits a peculiar feature of some cancer cells: they over-express their folate receptors, since they need lots of folic acid. The U-Michigan nanoparticles are designed to bind to the folate receptors, making it far more likely they will penetrate past the cell's natural protective barrier and release the therapeutic drug into the cell to kill it.
Experimental tests on lab mice showed that the targeted drug delivery was far more effective in killing cancer cells and diminishing tumors that the free-form injection of the same drug, with far fewer side effects. (Mice undergoing traditional chemotherapy typically die from the side effects, even though the therapy does imhibit tumor growth.)
There are some limitations. Different cancers have different biomarkers, so the folate-receptor target approach really only works with certain cancers. For instance, 90% of ovarian cancers over-express the folate receptor, compared to only 20% of lung cancers. Still, now that the proof of principle has been established, it's not hard to imagine a day when similar dendrimers could be made to target other biomarkers as well.
Another roadblock is possible toxicity. Those dendimers not absorbed by the cancer cells pass out of the body through the kidneys, in the urine. But the kidneys also have sections with especially high numbers of folate receptors, and may re-absorb some of the lethal folate-receptor-targeting drug, damaging the kidneys. There are still many more folate receptors in cancer cells, so chances are the risks are minimal, particularly when weighed against the benefits to be gained. But more tests will be performed to determine the exact levels of toxicity the human body can bear.
Ultimately, Baker would like to develop a therapeutic "smart cancer sensor," a single uber-nanoparticle that can pretty much do it all. First, it would target the affected site, bind to, and penetrate, cancer cells, and emit a telltale "signature" so doctors can tell where the cancer is located. Not only that, it would be able to measure the changes in the targeted cancer cells and select the appropriate therapeutic agent(s) based on those changes, then release the appropriate agent to kill the cancers. Lastly, it would be able to show doctors that the cancer cells were gone.
It's admittedly a tall order, but the progress to date has been encouraging enough to coax lots of much-needed funding, including $2.4 million from U-Michigan and $15 million from the National Cancer Institute. And yes, there's a spin-off start-up company dedicated to further developing the technology for eventual clinical use: Avidimer Therapeutic, in which Baker admits he has a significant financial investment. (How could he not? It is his technological nano-baby, after all.) Avidimer will need every penny of that funding to bring its fledgling product into actual clinical use: Baker estimates it will ultimately cost between $2.5 million to $4 million just to get things to the pre-clinical testing stage. The company has cleared most of the early regulatory hurdles, and Phase I trials are slated to being in August 2007.
The success of the U-Michigan/Avidimer technology inevitably raises the question of whether a similar approach might one day be employed to target other debilitating diseases, most notably Alzheimer's. One of the (many) reasons Alzheimer's is so difficult to treat is that it's difficult for drug molecules to penetrate the blood/brain barrier. It's one of the best protective mechanisms in the human body, but it also keeps out potentially helpful targeted drug therapies. Surely tiny nanoparticles might be able to penetrate it effectively?
Surprisingly, that's not the case, according to Baker -- at least not with their carefully tailored dendrimers. The only place the targeted drug didn't seem able to penetrate was the blood/brain barrier. There might be other nanoparticles developed in the future that prove capable of doing so, but to date, most such efforts have failed. Baker was also careful to emphasize that as ingenious and effective as his approach might be, nature is even smarter, and there's no telling what new ways cancer cells will find to take hold and proliferate in the human body in the future. We'll just have to keep one step ahead of it, I guess...
I've got to run back to the afternoon session on emerging materials and devices for nanoelectronics shortly. But stay tuned for more posts throughout the rest of the week, as blogging time (and Internet access) permits! As for Starbucks' new gingerbread latte: quite tasty, but the green tea latte still rules...
