Nanosized drug delivery systems take a leap forward
November 3, 2009
Blood vessels that supply tumors are more porous than normal vessels, makes nanoscale drug delivery systems a particularly attractive prospect. If properly engineered, nanoparticles can in fact get inside a tumor, targeting it precisely and allowing much higher drug dosages as they reduce side effects to a minimum. Two recent studies featured in the latest issue of the journal Nature Materials specifically address these issues and give us promising leads in the fight against cancer.
Gold cubic nanocages set off by light
Researchers at Washington University have come up with a hollow cubic nanostructure covered with a polymer that responds to light by letting the structure's content out. By filling the cages with chemotherapy drugs or other substances and then shining light on the targeted area on the patient's body, the system will allow to precisely deliver the drug where needed and reduce side effects significantly.
The release of the drug is triggered by near-infrared light with a wavelength between 750 and 900 nanometers, a window bordered on one side by wavelengths absorbed by blood and on the other by those absorbed by water: light in this range can penetrate several inches deep into the human body.
For the contents of the nanocages to be expelled, the structure also needs to exceed a critical temperature that, when reached, forces the polymer coating the nanostructure to shrink and collapse, opening small pores in the cage. This critical temperature is tunable and must be set to somewhere between the normal body temperature (37 °C) and the temperature at which heat starts killing living cells (42 °C).
The researchers tested the device by loading their nanocapsules with doxorubicin, a common chemotherapy drug, and triggered its release with a laser light, effectively killing breast cancer cells growing in wells on a plastic plate. By loading the cubes with an enzyme, the mechanism was also used to successfully kill a common kind of bacteria growing in the flora of our mouths and throats.
A group of bioengineers from Duke University has developed a nanoscale delivery system for cancer drugs and demonstrated that their formulation can eliminate tumors in mice after a single treatment.
The better targeting achieved by the system, along with the fact that the delivery vehicle breaks down into harmless byproducts, allowed the researchers to improve the maximum tolerated dosage by four times. This brought to visible improvements in treating tumors in mice, reducing the average tumor size by 25 times and doubling the average survival time compared to employing the drug (doxorubicin again) alone.
The delivery system developed by the team makes use of the bacterium E. coli, commonly used to produced proteins, but genetically altered to produce an artificial polypeptide known as a chimeric polypeptide.
When a drug and the polypeptide are put together, they spontaneously and consistently assemble into a water-soluble nanoparticle, meaning nanoparticles can be produced cheaply and in great quantities, regardless of the water-solubility of the drug by itself. This method, the researchers say, could theoretically be used to improve the effectiveness of other existing cancer drugs as well.
The researchers are now planning to test their combination on different types of cancer and tumors, and testing the effects of combining the chimeric polypeptides with other cancer drugs.