Toxicity of trastuzumab for breast cancer spheroids: Application of a novel on-a-chip concentration gradient generator

Evaluating the effectiveness of drugs on an individual basis before prescribing them has an influential role in choosing a successful treatment plan. The advent of microfluidic devices has provided us with more real plat-forms capable of mimicking the natural microenvironment (scales, shear stress, diffusion transport, etc.). This research has introduced a truncated microfluidic gradient maker that can create a linear concentration gradient of trastuzumab (showing good correlation (r(9) = 0.9968) with simulation data) with a wide range of flow rates (20-190 mu l/min) and investigate its effect on SK-BR-3 spheroid cells. The results of trastuzumab efficacy on 3D spheroid cells in the microchip were compared with the conventional 2D cell cultured by MTT assay at 24 h, 48 h, and 72 h. The results showed that trastuzumab had dose-dependent effects in both 2D and spheroid cell cultures. However, the IC50 values for trastuzumab were significantly higher in 2D cell culture (560 & PLUSMN; 23 mu g/ mL) compared to 3D spheroid models (407 & PLUSMN; 17 mu g/mL). Moreover, compared with conventional drug sensitivity tests, this microchip required fewer samples and reagents and a lower risk of fluctuation and contamination due to automatic medium exchange.

Automated summary

Evaluating the effectiveness of drugs on an individual basis before prescribing them is crucial in determining the right treatment plan. Microfluidic devices have emerged as a promising platform for mimicking natural microenvironments, allowing for more accurate drug testing. This study introduces a truncated microfluidic gradient maker that creates a linear concentration gradient of trastuzumab and investigates its effects on SK-BR-3 spheroid cells. The results show that trastuzumab has dose-dependent effects in both 2D and spheroid cell cultures, with lower IC50 values observed in the 3D spheroid models. Additionally, the microchip method requires fewer samples and reagents, reducing the risk of fluctuations and contamination.