Multidimensional viscoelastic mechanical indexes for assessing chemotherapeutic drug efficacy and chemoresistance

Assessing chemoresistance in cancer cells is crucial for chemotherapy treatment. Current assessment methods usually rely on biochemical reagents and are labour-intensive and time-consuming. Increasing evidence has revealed links between drug-induced changes in cell mechanical properties and cell viability. However, a method that can assess drug efficacy and chemoresistance using drug-induced variation in cellular mechanical parameters is still lacking.

MCF7 and MCF7/ADR breast cancer cells were incubated with doxorubicin (DOX), and the changes in viscoelastic mechanical parameters were measured using atomic force microscopy (AFM) indentation. The cell viability was measured using CCK-8 assays and fluorescence staining. Using support vector machine (SVM)-assessed mechanical separability, the classification index (σ) and drug resistance index (η) were proposed as mechanical indicators of drug efficacy and chemoresistance, respectively.

DOX treatment increased the elastic modulus, equilibrium elastic modulus and apparent viscosity of cells, and decreased the power-law exponent. The extent of these changes increased with DOX concentration. The consistent trends between σ and Mahalanobis distance, combined with Hotelling's T² significance analysis, supported σ as an indicator of mechanical-parameter separability. The changes in cell viability were consistent with changes in σ and η.

The σ values reflected drug efficacy, whereas η provided an indicator of chemoresistance. The proposed method offers a simple, rapid, and label-free complement to in vitro drug-sensitivity testing.