Guiding intracortical brain tumour cells to an extracortical cytotoxic hydrogel using aligned polymeric nanofibres

Abstract

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.

A biomaterial model of tumor stromal microenvironment promotes mesenchymal morphology but not epithelial to mesenchymal transition in epithelial cells

“…It was also observed that migration speed depended on ECM coating, where fibers with hyaluronic acid coating encouraged migration less than coatings with collagen-I, Matrigel or uncoated polycaprolactone. In another study by Jain et al, a laminin coating was used to facilitate glioblastoma migration along aligned, polycaprolactone nanofibers where migration was substantially more robust than along laminin-coated polymer film controls [41]. In our study, fibronectin or RGD peptide were used to coat the fibers to facilitate adhesion.…”

“…Recently, an aligned polymeric nanofiber sheet coated with laminin-1 was used to guide intracortical brain tumor cells to an extracortical cytotoxic hydrogel within a rat model of brain cancer (using human primary glioblastoma cells) [41]. These studies suggest a clinical use of aligned fibers to direct cancer cell migration for removal from the body.…”

Cancer research in need of a scientific revolution: Using ‘paradigm shift’ as a method of investigation

“…Application of the 'paradigm shift' method leads to a reversal of perspective in which cancer cells are no longer considered the target but the 'magic bullet' itself. This paradigm shift gave birth to the development of the cancer cell trap or tumour trap concepts, in which cancer cells are the 'bullets' that target a therapeutic trap where cancer cells are eliminated (van der Sanden et al 2013;Jain et al 2014). These are just a few examples illustrating the potential of the 'paradigm shift' as a method.…”

Spectral-optical Properties of Nutrient Coated Optical Fibers for Glioma Cells Growth Orientation

“…The new approach of such neoplasms type treatment is to control deep-lying brain tumor random proliferation by guiding tumor to the external surface where malignant cells could be registered and therapeutically affected without additional surgical intervention [1]. Neuro-scaffolds based on optical fibers structurally imitating white matter channels and blood vessels [2] seem to be promising for brain tumor cells growth orientation [3].…”