Cancer therapeutic study utilizing fluorescent bioimaging probe targeting tumor initiating cells

• Main Authors: Tan, Corrina Zi Ting, n
• Other Authors: -
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2023
• Subjects: Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/168377
• Institution: Nanyang Technological University

One of the top concerns regarding cancer therapy is possibility of cancer recurrence whereby cancer cells can develop resistance against certain treatments such as chemotherapy and radiation.1 These resistance cancer cells are often more aggressive, thus develop and metastasize a lot faster than primary tumors. Previously, tumor initiating cells (TIC) which have self-renewal and tumorigenic capabilities were identified. These TICs are also found to play a role in metastasis and recurrence in cancers but despite its dominance in cancer relapse, there is a lack of identification and treatment of TICs. Therefore, in this study, we are looking at a previously discovered small molecule probe specific for lung cancer TICs, TiNIR (Tumor Initiating cell probe with Near InfraRed), TiNIR binds to HMOX2 intracellularly, allowing us to identify TICs via its fluorescence signal. We demonstrated the effects of TiNIR on TS32 cells; its ability to identify TICs and at higher concentrations, exerting a cytotoxic effect on the TICs as well. Furthermore, we identified an efflux transporter which transports TiNIR out of the cell, reducing TiNIR’s identification and therapeutic ability on TS32 cells. Lastly, we also verified the efflux transporter functions through siRNA-mediated knockdown as well as inhibited its functions using 2 types of drugs: Verapamil and Cyclosporin A. The results obtained suggests that with a depletion of efflux transporter capabilities along with TiNIR treatment, it can identify and exerts a dual cytotoxic effect onto TICs. Thus, TiNIR can potentially serve as a viable therapeutic option to combat cancer recurrence in lung cancer.