Abstract
Purpose: Glioblastoma cells (GBM) that leave the tumor to infiltrate the brain cannot be removed by surgery, and they are frequently more resistant to chemo- and radiotherapy than healthy brain tissue. We are developing a trap in the form of a macroporous hydrogel that will be implanted in the surgical cavity after tumor removal. This gel will release a chemoattractant, CXCL12, in order to attract GBM cells which will enter the pores of the hydrogel. Once trapped, the GBM cells will be irradiated by stereotaxic radiosurgery. A higher dose of radiation can thus be delivered to the GBM cells, while preserving the brain cells at the periphery of the trap.
Materials and Methods: Hydrogels grafted with the cell adhesion peptide RGD (CGRGDS) were synthesized with different percentages of alginate and chitosan. These gels contained pores whose mean diameter was adjusted between 50 and 500 µm. The accumulation, retention and distribution of the GBM cells F98 were determined.
Results: The accumulation and retention of GBM cells (5 x 105) in the hydrogel were improved by grafting the cell adhesion peptide RGD to the surface of the pores at a density of 3.5 x 10-7 mol/400 mg of alginate. Addition of chitosan to an alginate hydrogel improved its structural stability in biological medium, and further increased the accumulation of GBM cells. The best distribution and accumulation of GBM cells in the hydrogels were obtained in those having pores with a diameter of 200 µm. A 3D migration system has demonstrated that GBM cells can migrate over a distance of 5 mm in 14 h and then accumulate in a hydrogel that releases the chemoattractant CXCL12 encapsulated in nanoparticles.
Conclusions: These results support testing this GBM cell trap in an animal model.
