�The trouble with victimization a shotgun to kill a housefly is that even if you catch the pesterer, you'll likely do a lot of damage to your home in the process. Hence the value of the more surgical flyswatter.
Cancer researchers have long faced a alike situation in chemotherapy: how to make the to the highest degree medication into the cells of a tumor without "spillover" of the medicinal drug adversely affecting the healthy cells in a patient's body.
Now researchers at Stanford University have addressed that problem using single-walled carbon nanotubes as rescue vehicles. The new method has enabled the researchers to pose a higher proportion of a given dose of medication into the tumor cells than is possible with the "free" do drugs - that is, the one non bound to nanotubes - thus reducing the amount of medication that they need to inject into a subject to achieve the desired therapeutic effect.
"That means you testament also give less drug reaching the normal tissue," said Hongjie Dai, professor of chemical science and senior author of a newspaper, which testament be published in the Aug. 15 issue of Cancer Research. So not only is the medication more effective against the tumor, troy ounce for oz., but it greatly reduces the side effects of the medicinal drug.
Graduate student Zhuang Liu is first-class honours degree author of the paper.
Dai and his colleagues worked with paclitaxel, a widely used cancer chemotherapy drug, which they employed against tumors cells of a type of breast cancer that were ingrained under the skin of mice. They found that they were able to get up to 10 times as much medication into the tumor cells via the nanotubes as when the standard formulation of the drug, called Taxol�, was injected into the mice.
The neoplasm cells were allowed to proliferate for about iI weeks prior to beingness treated. After 22 days of treatment, tumors in the mice treated with the paclitaxel-bearing nanotubes were on average less than half the size of those in mice treated with Taxol.
Critical to achieving those results were the size and surface structure of the nanotubes, which governed how they interacted with the walls of the blood vessels through which they circulated after organism injected. Though a tattling vessel - nautical or anatomical - is rarely a good thing, in this illustration the comparatively leaky walls of profligate vessels in the neoplasm tissue provided the opening that the nanotubes requisite to pillowcase into the tumor cells.
"The results are actually highly dependent on the surface chemical science," Dai said. "In other words, you don't get this final result just by attaching drugs to any nanotubes."
The researchers secondhand nanotubes that they had coated with polyethylene glycol (PEG), a common ingredient in cosmetics. The PEG they used was a form that has leash little branches sprouting from a primal trunk. Stuffing the trunks into the linked hexangular rings that make up the nanotubes created a visual gist that Dai described as looking like rolled-up chicken wire with feathers projecting out all over. The homespun sounding appearance notwithstanding, the nanotubes proved to be highly effective delivery vehicles when the researchers attached the paclitaxel to the tips of the branches.
Dai's team has found in earlier work (Proceedings of the National Academy of Sciences, Vol. 105, No. 5, 1410-1415, Feb. 5, 2008) that coating nanotubes with PEG was an effective way to keep the nanotubes circulating in the bloodstream for up to 10 hours, long enough to find their way to the fair game location and much yearner than give up medication would circulate. Although attaching the paclitaxel to the PEG turned out to slim down the circulation time, it proved to still be long sufficiency to deliver a highly effective dose inside the tumor cells.
All blood vessel walls are somewhat porous, just in intelligent vessels the pores are relatively small. By tinkering with the length of the nanotubes, the researchers were able to orient the nanotubes so that they were too large to get through the holes in the walls of normal blood vessels, but still small sufficiency to easily slip through the larger holes in the relatively leaky rake vessels in the tumor tissue.
That enabled the nanotubes to deliver their medicinal loading with tremendous efficiency, throwing a therapeutic wrench into the cellular means of reproduction and thus squelching the until now unrestrained proliferation of the tumor cells.
Dai aforementioned that the technique holds potential for delivering a range of medications and that it may as well be possible to grow ways to channel the nanotubes to their target even more precisely.
"Right now what we ar doing is so-called 'passive targeting,' which is using the leaky vasculature of the tumor," he said. "But a more than active targeting would be attaching a peptide or antibody to the carbon nanotube drug, matchless that will bind more specifically to the tumor, which should further enhance the treatment efficacy."
Dai's team is already at work development more targeted approaches, and he is optimistic about the electric potential applications of nanotubes.
"We are emphatically hoping to be able to push this to practical applications into the clinic. This is one step onward," he said. "But it will still take time to sincerely prove the efficacy and the safety."
The work was funded by the NIH-National Cancer Institute Center for Cancer Nanotechnology Excellence Focused on Therapeutic Response at Stanford, a Stanford Bio-X Initiative Grant, NIH-National Cancer Institute Grant and a Stanford Graduate Fellowship. Collaborators on this work included Assistant Professor Shawn Chen's grouping in the Stanford Department of Radiology.
-- Link to paper in Cancer Research
-- Link to February PNAS theme
Source - Louis Bergeron
Stanford University
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