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Potential new drug delivery system

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August 31, 2009

Co-authors Tambet Teesalu and Kazuki N. Sugahara proudly display their laboratory-develope...

Co-authors Tambet Teesalu and Kazuki N. Sugahara proudly display their laboratory-developed drug-delivery system

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Scientists at UC Santa Barbara have developed a biological mechanism that can act as an entirely new means of drug delivery, carrying with it the potential to make treating illness even more effective. Rather than simply circulating in the bloodstream, the laboratory-developed peptide can deliver nanoparticles directly into tissue.

Senior author Erkki Ruoslahti of the Burnham Institute for Medical Research at UCSB explains, “when giving a drug to a patient, it circulates in the bloodstream, but often doesn’t get into the tissue. This is especially true with tumors.”

Ruoslahti’s team conducted a study using prostate cancer cells to determine whether the peptide, essentially a small piece of protein they developed, could successfully transport “cargo” to the targeted cancer tissue. Like a passenger on a bus arriving at its destination, the cargo - in this case drug nanoparticles or even other cells - exits the blood vessel and then goes about its business, which is to penetrate the target tissue.

How the peptide understands where and when to dislodge its cargo is embedded in its design. The peptide has a built-in exit, known as a “C terminal” which contains the “motif”—an amino acid sequence that causes tissue penetration. Like a door, the “C terminal” must be open for the drug to penetrate the tissue. The peptide’s success in delivering its cargo hinges on this fact. So reliant is this delivery system on the “C terminal” that the team have coined it the “C-end rule,” or CendR, pronounced “sender.”

As important a component as the CendR is, it is not without flaw. It ushers in life-saving drugs to treat sick tissue, but it also acts as a gateway for potentially life-threatening viruses to hijack cells. According to Ruoslahti, the CendR is “a natural system. We’re not quite clear what its exact function is, but viruses appear to take advantage of it.”

Exactly how viruses use this system requires further research so that inhibitors can be developed to prevent viruses from entering the cell. The results of this study are published in Proceedings of the National Academy of Sciences.

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