Characterizing for Subcellular Physical Property Changes of Chemotherapy Drug-Resistant Malignant Cancer Cells

Recently, scanning ion conductance microscopy (SICM) as a noncontact nanoprobe tool has offered great advantages for applications in revealing biophysicochemical properties of soft biological samples, specifically for living cells. These physical properties, e.g., stiffness, of the cell surface provide an efficient label-free biomarker for differing tumor from normal cells, leading to gradually increasing interest in cancer biological studies. However, expanding potential application of SICM for cancer treatment, especially targeting chemotherapy facing a challenge in drug resistance, is still rarely explored. In addition, in biology, some clues indicate that the physical factors (matrix stiffness and stress) can contribute to tumor drug resistance. Meanwhile, fundamental studies to quantify these unique physical properties of drug-resistant cancer cells correlated with leverage for targeted therapy are less known. Here, we utilized chemotherapy drugs, 5-fluorouracil (5-FU) and oxaliplatin (OXA), to establish three drug-resistant cell lines from human colorectal cancer, including DLD1, SW620, and HT29 cells. High-speed SICM measurements were performed to visualize surface characteristics of subcellular physical properties (heights, roughness, and stiffness) on the control (ctrl) sample and drug-resistant samples derived from ctrl samples. Statistical analysis of stiffness showed a reduced change from drug-resistant samples, especially those resistant to 5-FU and OXA simultaneously, in comparison to ctrl samples. This work sheds light on subcellular physical properties of drug-resistant cell lines. The SICM technique as an important strategy would provide useful assistance in biomedicine in leveraging for targeted therapy.