New Packaging Revives Potential for Highly Toxic Cancer Drug

This coating prevented the premature disintegration of the 3BrPA drug molecules and safeguarded healthy tissue from the drug's toxic effects.

Phase-contrast microscopy, bioluminescence imaging (BLI), zymography, and Matrigel assays were used to characterize the effects of the drug in vitro. In vivo effects were studied by using the encapsulated drug to treat a mouse model carrying human pancreatic tumor xenografts.

Results of the Matrigel invasion assay as well as zymography published in the October 17, 2014, online edition of the journal Clinical Cancer Research revealed that the encapsulated drug showed anti-invasive effects in sub-lethal concentrations. In vivo, animals treated with the encapsulated 3BrPA demonstrated minimal or no tumor progression as evident by the BLI signal as opposed to control animals treated with the drug gemcitabine or with only the cyclodextrin. In contrast to animals treated with free 3-BrPA, no lethal toxicity was observed for the encapsulated drug.

“We developed 3BrPA to target a hallmark of cancer cells, namely their increased dependency on glucose compared with normal cells. But the nonencapsulated drug is toxic to healthy tissues and inactivated as it navigates through the blood, so finding a way to encapsulate the drug and protect normal tissues extends its promise in many cancers as it homes in on tumor cells,” said senior author Dr. Jean-Francois Geschwind, professor of radiology at Johns Hopkins University. “The extremely promising results of the study make the encapsulated drug a good candidate for clinical trials, particularly for patients with pancreatic ductal adenocarcinoma.”

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