Nanoscale Quantifying the Effects of Targeted Drug on Chemotherapy in Lymphoma Treatment Using Atomic Force Microscopy

Abstract

The applications of targeted drugs in treating cancers have significantly improved the survival rates of patients. However, in the clinical practice, targeted drugs are commonly combined with chemotherapy drugs, causing that the exact contribution of targeted drugs to the clinical outcome is difficult to evaluate. Quantitatively investigating the effects of targeted drugs on chemotherapy drugs on cancer cells is useful for us to understand drug actions and design better drugs. The advent of atomic force microscopy (AFM) provides a powerful tool for probing the nanoscale physiological activities of single live cells. In this paper, the detailed changes in cell morphology and mechanical properties were quantified on single lymphoma cells during the actions of rituximab (a monoclonal antibody targeted drug) and two chemotherapy drugs (cisplatin and cytarabine) by AFM. AFM imaging revealed the distinct changes of cellular ultra-microstructures induced by the drugs. The changes of cellular mechanical properties after the drug stimulations were measured by AFM indenting. The statistical histograms of cellular surface roughness and mechanical properties quantitatively showed that rituximab could remarkably strengthen the killing effects of chemotherapy drugs. The study offers a new way to quantify the synergistic interactions between targeted drugs and chemotherapy drugs at the nanoscale, which will have potential impacts on predicting the efficacies of drug combinations before clinical treatments.