Glioblastoma multiforme is an aggressive, invasive brain tumour with a poor survival rate. Available treatments are ineffective and some tumours remain inoperable because of their size or location. The tumours are known to invade and migrate along white matter tracts and blood vessels. Here, we exploit this characteristic of glioblastoma multiforme by engineering aligned polycaprolactone (PCL)-based nanofibres for tumour cells to invade and, hence, guide cells away from the primary tumour site to an extracortical location. This extracortial sink is a cyclopamine drug-conjugated, collagen-based hydrogel. When aligned PCL-nanofibre films in a PCL/polyurethane carrier conduit were inserted in the vicinity of an intracortical human U87MG glioblastoma xenograft, a significant number of human glioblastoma cells migrated along the aligned nanofibre films and underwent apoptosis in the extracortical hydrogel. Tumour volume in the brain was significantly lower following insertion of aligned nanofibre implants compared with the application of smooth fibres or no implants.
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We would like to thank J. Leisen for his technical expertise with the MR scanner and J. Lyon and S. Nayebosadri for their assistance with the animal surgeries and immunohistochemistry. We would also like to acknowledge funding support for this project from National Institutes of Health EUREKA R01 CA153229 (NCI) (R.V.B.), the Georgia Research Alliance (R.V.B.), and Ian’s Friends Foundation (R.V.B.)
The authors declare no competing financial interests.
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Jain, A., Betancur, M., Patel, G. et al. Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres. Nature Mater 13, 308–316 (2014). https://doi.org/10.1038/nmat3878
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