The standard of care therapy of glioblastoma (GBM) includes invasive surgical resection, followed by radiotherapy and concomitant chemotherapy. However, this therapy has limited success, and the prognosis for GBM patients is very poor. Although many factors may contribute to the failure of current treatments, one of the main causes of GBM recurrences are glioma stem cells (GSCs). This review focuses on nanomedicine strategies that have been developed to eliminate GSCs and the benefits that they have brought to the fight against cancer. The first section describes the characteristics of GSCs and the chemotherapeutic strategies that have been used to selectively kill them. The second section outlines the nano-based delivery systems that have been developed to act against GSCs by dividing them into nontargeted and targeted nanocarriers. We also highlight the advantages of nanomedicine compared to conventional chemotherapy and examine the different targeting strategies that have been employed. The results achieved thus far are encouraging for the pursuit of effective strategies for the eradication of GSCs.

Orthotopic glioblastoma xenografts are paramount for evaluating the effect of innovative anti-cancer treatments. In longitudinal studies, tumor growth (or regression) of glioblastoma can only be monitored by noninvasive imaging. For this purpose, bioluminescence imaging (BLI) has gained popularity because of its low cost and easy access. In the context of the development of new nanomedicines for treating glioblastoma, we were using luciferase-expressing GL261 cell lines. Incidentally, using BLI in a specific GL261 glioblastoma model with cells expressing both luciferase and the green fluorescent protein (GL261-luc-GFP), we observed an apparent spontaneous regression. By contrast, the magnetic resonance imaging (MRI) analysis revealed that the tumors were actually growing over time. For other models (GL261 expressing only luciferase and U87 expressing both luciferase and GFP), data from BLI and MRI correlated well. We found that the divergence in results coming from different imaging modalities was not due to the tumor localization nor the penetration depth of light but was rather linked to the instability in luciferase expression in the viral construct used for the GL261-luc-GFP model. In conclusion, the use of multi-modality imaging prevents possible errors in tumor growth evaluation, and checking the stability of luciferase expression is mandatory when using BLI as the sole imaging modality.