A novel 3D polycaprolactone high-throughput system for evaluation of toxicity in normoxia and hypoxia

Two-dimensional (2D) culturing of cancer cells has been indispensable for the development of anti-cancer drugs. Drug development, however, is lengthy and costly with a high attrition rate, calling to mind that 2D culturing does not mimic the three-dimensional (3D) tumour microenvironment in vivo. Thus, began the development of 3D culture models for cancer research. We have constructed a 3D 96-well plate using electrospun fibres made of biocompatible polycaprolactone (PCL). Finely-cut PCL fibre pieces in water/ethanol solution was pipetted to the wells of hydrophobic 96-well plates. A fibrous network of approximately 200 mu m thickness and high porosity was formed after crosslinking and drying. Human JIMT-1 breast cancer cells or fibroblasts were seeded into the network. Confocal microscopy shows that the cells grow throughout the fibre network. The toxicity of paclitaxel and an experimental salinomycin analogue was assessed and compared in 2D and 3D cultures incubated under conditions of normoxia and hypoxia often found in tumours. The toxicity of both compounds is lower when the cells are cultured in 3D compared to 2D in either normoxia or hypoxia. We conclude that our 96-well assay is a cost-efficient tool that may be used for high-throughput pre-clinical screening of potential anti-cancer compounds.

Automated summary

The translation describes the importance of two-dimensional (2D) culturing for cancer drug development, but highlights the limitations due to not mimicking the in vivo three-dimensional (3D) tumor microenvironment. The development of a 3D culture model using electrospun fibres made of biocompatible polycaprolactone (PCL) is explained, along with the observation of lower toxicity of anti-cancer compounds in 3D cultures compared to 2D, suggesting the potential use of a cost-efficient 96-well assay for pre-clinical screening.