Researchers in South Korea have developed a magnetic 'switch' that induces apoptosis of colon cancer cells in vitro, and have also shown that this technology can be applied in vivo in a zebrafish model. The research, published in Nature Materials, raises the possibility of new targeted anticancer therapies that could potentially avoid p53 mutation-induced drug resistance.
A team from Yonsei University, Seoul, South Korea, constructed magnetic nanoparticles conjugated to a death receptor 4 (DR4)-specific antibody. Once the nanoparticles were bound to DR4-expressing colon cancer cells, a magnetic field was applied and the receptors were shown to form densely populated aggregates. This receptor clustering promoted extrinsic apoptosis signalling pathways; within 24 hours around 50% of the treated cells were dead, whereas the untreated cells remained viable. In vivo, the magnetic switch was shown to cause morphological alterations in the tail region of zebrafish — a sign of apoptosis.
Andrew MacKay of the University of Southern California, USA, said “They've identified a major opportunity for magnetic nanoparticles ... This might be a new way to do really targeted therapeutics” ( ScienceNews , 9 Oct 2012). However, Henry Scowcroft of Cancer Research UK cautioned that although fascinating, this was still “extremely preliminary research [with] a long way to go before it's ready to test in humans” ( Mail Online , 8 Oct 2012). Concerns about the efficacy of the nanoparticles in drug-resistant cells were also raised by Courtney Broaddus of the University of California, USA, although she concluded, “it's very intriguing, the potential applications of this technology” ( ScienceNews , 9 Oct 2012).
The team now plan to extend their research to different types of cancer cells, as well as to other clinically useful membrane receptor targets.
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Rodwell, C. Fatal attraction. Nat Rev Cancer 12, 735 (2012). https://doi.org/10.1038/nrc3389
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DOI: https://doi.org/10.1038/nrc3389