Editors' ChoiceNanomedicine

Taking the Fight Outside

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Science Translational Medicine  05 Mar 2014:
Vol. 6, Issue 226, pp. 226ec41
DOI: 10.1126/scitranslmed.3008714

It is usually a death sentence when a tumor does not respond to therapy and cannot be surgically removed. What if instead of taking the fight to the tumor, the cancer cells came outside? Now, Jain et al. may have a solution: a device that mimics the natural cues for cancer cell migration and essentially “drains” the tumor off of malignant cells, taking the fight away from the original tumor site.

Human glioblastoma cells (U87MG) form highly aggressive brain tumors by migrating along white-matter tracts and blood vessels and invading surrounding tissue. The authors engineered millimeter-sized polymer conduits that contained sheets with polycaprolactone-based fibers to act as migratory cues for the cancer cells. Jain and colleagues first built an in vitro model of the system, in which two wells filled with collagen were separated by a channel covered with laminin-coated nanofibers. The glioblastoma cells from the “source” (mimicking the tumor site) migrated along the nanofiber-coated surface toward the “sink” (a well functionalized with cyclopamine—an antitumor drug). Upon entering the sink, the cancer cells apoptosed. The authors also found that cyclopamine had minimal adverse effects on healthy cortical neurons and astrocytes. The conduits were then implanted in the rat brain harboring human U87MG tumors, with one end terminating near the tumor boundary and the other connected to a therapeutic, extracortical cyclopamine sink. Similar to in vitro studies, the glioblastoma cells migrated away from the tumor site, toward the cancer-killing sink. The authors saw that this shrunk the tumors, with minimal migration along the outside smooth surface of the conduit, suggesting that the conduit prevented them from spreading throughout the brain as they moved toward the sink.

Overall, this is an approach with translational potential for treating malignant tumors at cortical sites unfavorable for surgical removal, such as speech and motor areas. Before the technology is ready for the clinic, animal studies should evaluate the efficacy of this therapeutic technique on long-term survival rates and optimize the implementation of the extracortical device in humans, with an emphasis on preventing possible infection and use of other chemotherapeutics if cyclopamine is not well tolerated.

A. Jain et al., Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres. Nat. Mater., published online 20 February 2014 (10.1038/nmat3878). [Abstract]

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