Quantum Carbon: A New Approach Towards Label-Free Cancer Stem Cell Theranostics

Abstract

<p>The primary objective of this thesis is to develop sub 10 nm carbon-based nanoprobes with a potential for detection, monitoring, and treating cancer. The carbon-based nanoprobes were synthesized using ultrashort pulsed laser through the multiphoton ionization process. Early detection of cancer is critical for therapeutic success. Current cancer theranostics primarily focus on cancer cells with a high proliferation rate, whereas recent studies have revealed cancer stem cells (CSC) as the reason for therapeutic failure. The predominant role of CSCs in cancer metastases makes them a clinically relevant target for cancer theranostics. However, existing methods of in vitro detection of CSC are depends on cancer – specific surface markers, which limits the universal application of the detection method. Hence, there exists a need for an ultrasensitive diagnostic method that is used for the detection of CSC irrespective of their tissue origin. In this thesis, the developed sub 10nm carbon nanoprobes were employed for ultrasensitive detection of CSC using SERS. The 3-D quantum Sensor based on graphene oxide, a new phenomenon of single molecule –SERS sensing with an ability to replace plasmonic materials. The next study introduces a unique concept of precisely shrinking a carbon-based organic semiconductor probe, which is used for tag-free genomic DNA detection. Following the single molecule detection, the sub 10nm carbon probes were applied for intracellular detection of cancer, demonstrated by detection of cancer cells, CSC and tumorigenic CSC down to single cellular level. The ability to detect CSC in its fundamental niche provides an insight into the evolution and maintenance of CSC, thereby providing a wholistic detection method of cancer stem cell by probing both the phenotypic and metabolic attributes of CSC. Building upon the efficient detection of CSC and tumorigenic CSC, a self- functionalized CSC theranostic probe was utilized to monitor cancer stem cells and induce therapeutic differentiation through metabolic reprogramming of CSC.</p> <p>The research performed in this thesis demonstrates a unique carbon-based nanomaterial with different configurations, that can detect CSC down to single cellular level. The contribution rendered towards the synthesis, application, and manipulation of the carbon-based nanomaterials marks the fundamental step towards the early diagnosis, real-time tracking of cancer prognosis non-invasively, and a realizable platform for CSC targeted theranostics.</p>