New targeted therapy for lung cancer using precious metals as Trojan exosomes

By Samantha Black, PhD, The Science Advisory Board staff writer

September 9, 2019 -- Researchers at the University of Edinburgh and the Universidad de Zaragoza in Spain present a novel therapeutic approach to treating cancer on September 9. The research using exosome-directed catalyst prodrug therapies was published in Nature Catalysis.

Palladium (Pd) has long been used in catalytic converters to detoxify exhausts in many vehicles. Now, bioorthogonal scientists are investigating how to selectively deliver Pd catalysts to cancer cells and deliver targeted drugs. Professor Asier Unciti-Broceta, from the University of Edinburgh's Cancer Research UK Edinburgh Centre, said: "We have tricked exosomes naturally released by cancer cells into taking up a metal that will activate chemotherapy drugs just inside the cancer cells, which could leave healthy cells untouched."

The new study exploits Pd’s ability to produce xenobiotics and uncaging biomolecules in living systems, mimicking how some viruses cross cell membranes to spread infection. Researchers built a bioartificial device comprising cancer-derived exosomes that are loaded with Pd catalysts by a method that enables the controlled assembly of Pd nanosheets directly inside the vesicles. The hybrid system mediates Pd-triggered dealkylation reactions in vitro and inside cells, and displays preferential tropism for their progenitor cells.

The bioartificial system was tested in lung cancer cells and cells associated with glioma (tumors in the brain and spinal cord). Exosomes were derived from these cancer cells and subsequently loaded with Pd catalysts. The artificial exosomes acted as Trojan horses, working in tandem with existing cancer drugs – in this case, Panobinostat – which were delivered straight to primary tumors and metastatic cells.

Having proved the concept in laboratory tests, the researchers have now been granted a patent that gives them exclusive rights to trial palladium-based therapies in medicine. The study was funded by the Engineering and Physical Sciences Research Council and the European Research Council.

Professor Jesús Santamaría, of the Universidad de Zaragoza, said: "This has the potential to be a very exciting technology. It could allow us to target the main tumor and metastatic cells, thus reducing the side effects of chemotherapy without compromising the treatment."

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