Efficacy of molecular and nano-therapies on brain tumor models in microfluidic devices

The three-dimensional (3D) organization of cells affects their mobility, proliferation, and overall response to treatment. Spheroids, organoids, and microfluidic chips are used in cancer research to reproduce in vitro the complex and dynamic malignant microenvironment. Herein, single-and double-channel microfluidic devices are used to mimic the spatial organization of brain tumors and investigate the therapeutic efficacy of molecular and nano anti-cancer agents. Human glioblastoma multiforme (U87-MG) cells were cultured into a Matrigel matrix embedded within the microfluidic devices and exposed to different doses of free docetaxel (DTXL), docetaxel-loaded spherical polymeric nanoparticles (DTXL-SPN), and the aromatic N-glucoside N-(fluorenylmethox-ycarbonyl)-glucosamine-6-phosphate (Fmoc-Glc6P). We observed that in the single-channel microfluidic device, brain tumor cells are more susceptible to DTXL treatment as compared to conventional cell monolayers (50-fold lower IC50 values). In the double-channel device, the cytotoxicity of free DTXL and DTXL-SPN is comparable, but significantly lowered as compared to the single-channel configuration. Finally, the administration of 500 mu M Fmoc-Glc6P in the double-channel microfluidic device shows a 50 % U87-MG cell survival after only 24 h, and no deleterious effect on human astrocytes over 72 h. Concluding, the proposed microfluidic chips can be used to reproduce the 3D complex spatial arrangement of solid tumors and to assess the anti-cancer efficacy of thera-peutic compounds administrated in situ or systemically.

Automated summary

The 3D organization of cells plays a significant role in their behavior and response to treatment. In cancer research, spheroids, organoids, and microfluidic chips are used to mimic the complex microenvironment of tumors. This study utilized microfluidic devices to replicate the spatial organization of brain tumors and evaluate the efficacy of anti-cancer agents. The results showed that brain tumor cells were more sensitive to treatment in the microfluidic device compared to traditional cell cultures. The proposed microfluidic chips can effectively reproduce the 3D structure of tumors and assess the effectiveness of therapeutic compounds.