New method allows first-ever delivery of highly toxic cancer drug

Senior author Santosh Kesari, UCSD director of neuro-oncology--Courtesy of UCSD

When it comes to delivering cancer drugs, there is always a double-edged sword. Too potent a compound, and you risk harming healthy tissue along with tumor cells; too weak a drug, and you need to up the dose to reach a desired outcome. By using encapsulation methods that allow cancer drugs to travel safely in the bloodstream and still deliver a toxic payload to tumors, however, side effects can be greatly reduced.

So to safely deliver the very powerful anti-cancer compound staurosporine (STS), researchers at the University of California, San Diego School of Medicine have developed a liposome-based method to stabilize the drug and encapsulate it on its way to cancerous cells. STS, originally isolated from a bacterium in 1977, according to a UCSD report, causes apoptosis (programmed cell death) and for more than 35 years has been too strong for use as a cancer drug.

The UCSD scientists published in the International Journal of Nanomedicine online this week that, for the first time, they have safely delivered the STS compound to mouse tumors with no apparent side effects using hollow, spherical liposomes as a delivery vehicle. They tracked the penetration with fluorescence and confirmed the lower toxicity by noting the animals' stable weight.

The researchers were also able to load each liposome with 70% more STS than ever before, aided by pH-manipulating technology developed at UC San Diego's Moores Cancer Center.

"By itself, staurosporine shows potent activity against a number of cancer cell lines, including chemotherapy-resistant tumors," senior author Santosh Kesari said in a statement. "However, it also harms normal tissue. With this study, we have been able to overcome the pharmacokinetic barriers to delivering staurosporine tumors with the use of liposomes."

"Staurosporine is able to drive virtually any mammal cell into apoptosis," added project scientist Milan Makale. "It is able to uniquely interfere with several cell signaling pathways, even in cancer cell lines that defy frontline chemotherapy agents. In the case of treatment-resistant brain, colon or pancreatic cancers, the potency of staurosporine stacks the odds in our favor of improving current treatments and outcomes. With an appropriately engineered liposomal delivery system, we can finally keep the drug in the blood longer, get it into the tumor better, and to a significant degree, spare healthy tissue."

- here's the UCSD report

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