Prediction of Cancer Stem Cell Fate by Surface-Enhanced Raman Scattering Functionalized Nanoprobes.

Abstract

Cancer stem cells (CSCs) are the fundamental building blocks of cancer dissemination, so it is desirable to develop a technique to predict the behavior of CSCs during tumor initiation and relapse. It will provide a powerful tool for pathological prognosis. Currently, there exists no method of such prediction. Here, we introduce nickel-based functionalized nanoprobe facilitated surface enhanced Raman scattering (SERS) for prediction of cancer dissemination by undertaking CSC-based surveillance. SERS profiling of CSCs of various cell lines (breast cancer, cervical cancer, and lung cancer) was compared with their cancer counterparts for the prediction of prognosis, with statistical significance of single-cell sensitivity. The single-cell sensitivity is critical as even a few CSCs are capable of initiating a tumor. Intermediate states of CSC transmutation to cancer cells and its reverse were monitored, and nanoprobe-assisted SERS profiling was undertaken. We experimentally demonstrated that the <i>quasi</i>-intermediate CSC states have dissimilar profiles during the transformation from cancer to CSC and <i>vice versa</i> enabling statistical differentiation without ambiguity. It was also observed that molecular signatures of these opposite pathways are cancer-type specific. This observation provided additional clarity to the current understanding of relatively unfamiliar <i>quasi</i>-intermediate states; making it possible to predict CSC dissemination for variety of cancers with ∼99% accuracy. Nano probe-based prediction of CSC fate is a powerful prediction tool for ultrasensitive prognosis of malignancy in a complex environment. Such CSC-based cancer prognosis has never been proposed before. This prediction technique has potential to provide insights for cancer diagnosis and prognosis as well as for obtaining information instrumental in designing of meaningful CSC-based cancer therapeutics.