Quantifying Anticancer Drug Doxorubicin Binding to DNA using Optical Tweezers

Abstract

Doxorubicin is a successful anticancer drug approved for use in the 1970s and is considered to be one of the most effective cancer treatment methods today. Although Doxorubicin has positive survival statistics it has very negative side effects in many cases. Bleeding from the soles of the palms and feet, along with excruciating pain is often exhibited through the administration of this drug. Based on the preliminary findings utilizing optical tweezers we anticipate that this study will provide critical information about the drug binding mechanism. Single molecule biophysics techniques have provided useful insight into the DNA-binding mechanisms of small molecules. For this reason, in this study we quantify the binding kinetics and affinity of Doxorubicin to DNA using optical tweezers. The optical tweezers allow us to trap a single DNA molecule and manipulate it in the presence of various concentrations of Doxorubicin. Preliminary results suggest that DNA melting facilitates the intercalation process in the nanomolar range, implying a higher binding strength than the previously reported micromolar range.