Photothermal ablation of malignant brain tumors by nanoparticle loaded macrophages

Introduction: Nanoshells are a new class of optically tunable nanoparticles composed of a dielectric core (silica) coated with an ultrathin metallic layer (gold). Since nanoshells are roughly one million times more efficient at converting NIR light into heat than conventional dyes when exposed to NIR light, they can generate sufficient heat to induce cell death. Macrophages are frequently found in and around glioblastomas in both experimental animals and patient biopsies. Inflammatory cells loaded with nanoparticles could therefore be used to target tumors. Materials and Methods: Human brain tumor spheroids were co-incubated with fluorescent labeled mitomycin treated murine Ma (P388-D) loaded with increasing numbers of gold nanoshells. The spheroids were exposed to increasing levels of NIR (810 nm) light, corresponding to the absorption peak of the nanoshells. The effect of the radiation treatment was evaluated by live/dead assay examined by two photon microscopy and the kinetics of spheroid growth in a 2 week period. Results: Nanoshell loaded macrophages were capable of invading preformed spheroids following 12hrs of co-incubation. Significant cell death within the spheroids containing nanoshell loaded macrophages was observed following NIR light exposure. Spheroids treated in this manner also showed no tendency to further growth. In contrast spheroids containing macrophages alone (no nanoshell incorporation), exposed to similar levels of NIR light, showed a growth pattern similar to non-treated controls and contained a majority of living tumor cells. Conclusion: The in vitro results of macrophage-mediated delivery of nanoshells into malignant brain tumor spheroids suggest that photothermal ablation of GBM may be possible. Animal experiments on tumor bearing rats are presently underway to examine this possibility further.