Researchers use click chemistry for cancer drug delivery

Australian researchers are making things click for improved drug delivery by employing click chemistry to coat polymer capsules with antibodies tuned to stick to cancer cells. The result, researchers say, is to transport drugs directly to diseased cells while sparing the surrounding healthy cells. At times we sound like a broken record, but this kind of targeted attack against cancer is exactly what drug-delivery research is all about these days.

Frank Caruso at the University of Melbourne--along with colleagues at the CSIRO and the Ludwig Institute for Cancer Research in Australia--chose antibodies that bind to the A33 antigen, which is found on the surface of more than 95 percent of primary and metastatic colorectal cancers, according to a report in Nature Asia Materials. The resulting antibody-capsule complex proved to be highly effective at attaching to cancer cells that expressed A33, even when those cells were greatly outnumbered by cells without the antigen. "The capsules could target the cancer cells even when they were present as only 0.1% of the total cell population," Caruso is quoted as saying.

The researchers ran into some trouble when they turned to click chemistry to attach the antibodies to the capsules. They used a copper-catalyzed reaction to attach one molecule bearing an azide group to another functionalized with an alkyne. But when copper was added, the antibody started to clump. So, they partially masked the copper with a chelator molecule, which prevented the copper from interacting with the antibodies but still allowed it to catalyze the click reaction. This made the capsules highly selective cancer-seeking agents. "Using a chelator to prevent aggregation of the antibodies during the coupling reaction was the principal breakthrough in the project," Angus Johnston, a member of the University of Melbourne team, told Asia Materials.

- read all about it in Asia Materials

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