Determination of chemoresistance in ovarian cancer by simultaneous quantification of exosomes and exosomal cisplatin with surface enhanced Raman scattering

Abstract

Ovarian cancer is one of the most prevalent and lethal cancers in the world. This disease is frequently associated with a resistance to conventional chemotherapy, often acquired during therapy. We report a new method of diagnosing chemoresistance in ovarian cancers by simultaneous quantification of tumor derived exosomes and the chemotherapy drug cisplatin excreted within them. This is accomplished by a surface enhanced Raman scattering modality using cysteine capped gold nanoparticles. Interaction between the nanoparticles and cisplatin causes the nanoparticles to become destabilized, and the rate of this aggregation is proportional to the concentration of the drug. The exosome spectra were subsequently used to develop regression and discriminant models using support vector machines (SVM), which were used to differentiate between histological subtypes of ovarian cancer and their chemoresponsiveness. This method is able to measure exosome-derived cisplatin down to a concentration of 0.17 µg/mL, and exosomes down to 65 nM. Combining these metrics with support vectors machine discriminant models is able to diagnose chemoresistance with greater than 90% accuracy.