Microfluidic chip for synergic drugs assay in 3D breast cancer cell

Abstract

Some anticancer treatments may cause Multidrug Resistance (MDR). In these cases, cells pump the drug out of the intracellular environment, thereby preventing drug effects. Several strategies have been used to avoid MDR, including using two or more drugs at low concentrations to increase the sensitivity of cells to treatment. We present an effective, cheap, fast microfluidic alternative to test two drugs simultaneously using a reversible sealing and reusable device to determine the optimal concentration. We used the rugs doxorubicin (DOX) and paclitaxel (PXT) as proof of concept. The microdevice allows the testing of two drugs in real time. Furthermore, running two experiments in sextuplicates and control in the same microchip is possible. We used two combinations of drugs, varying the drug concentration (C₁ = 0.010 mg.mL^− 1 DOX and 0.002.mL^− 1 mg PXT, C₂ = 0.010 mg.mL^− 1 DOX and 0.004 mg.mL^− 1 PXT), and evaluated cell death over time. The intermediate drug concentrations were more efficient, reducing the time required to decrease the viability of breast tumor cells, MCF-7 (C₁ = 180 and C₂ = 120). In further analysis, the microdevice also allowed characterization of the effects of the drugs (antagonist, synergic, or additive). This microdevice is a reliable tool for estimating the different combinations of two drug concentrations in a single assay simply and quickly.