The New Jersey Institute of Technology's
Electronic Theses & Dissertations Project

Title:	Mitochondria imaging and targeted cancer treatment
Author:	Zhao, Tinghan
View Online:	njit-etd2019-080 (xv, 98 pages ~ 0.0 MB pdf)
Department:	Department of Chemistry and Environmental Science
Degree:	Doctor of Philosophy
Program:	Chemistry
Document Type:	Dissertation
Advisory Committee:	Belfield, Kevin D. (Committee chair) Haorah, James (Committee member) Kim, Yong Ick (Committee member) Li, Mengyan (Committee member) Zhang, Yuanwei (Committee member)
Date:	2019-12
Keywords:	Cancer Cell imaging Chemoresistance Mitochondria Therapy
Availability:	Unrestricted
Abstract:	Mitochondria are essential organelles as the site of respiration in eukaryotic cells and are involved in many crucial functions in cell life. Dysfunction of mitochondrial metabolism and irregular morphology have been frequently found in human cancers. The capability of imaging mitochondria as well as regulating their microenvironment is important both scientifically and clinically. Mitochondria penetrating peptides (MPPs), certain peptides that are composed of cationic and hydrophobic amino acids, are good candidates for mitochondria targeting. Herein, a novel MPP, D-argine-phenylalanine-D-argine-phenylalanine-D-argine-phenylalanine-NH2 (rFrFrF), is conjugated with a rhodamine-based fluorescent chromophore (TAMRA). The TAMRA-rFrFrF probe exhibits advantageous properties for long-term mitochondria tracking of up to three days with low cytotoxicity and high biocompatibility. Mitochondria isolation experiments further confirmed the mitochondria targeting of the TAMRA-rFrFrF probe with minimal perturbation of mitochondrial function. Mitochondrial function and metabolism are centrally involved in cancer initiation, tumorigenesis, growth, survival, and metastasis. Dysfunction of mitochondria, especially mitochondrial membrane hyperpolarization, plays a key role in drug resistance during cancer treatment. We report a boron-dipyrromethene (BODIPY) triarylsulfonium-based molecule (BD-PAG) as an opto-biomodulator (MOB) to target mitochondria and modulate mitochondrial pH. Significantly, our BD-PAG MOB demonstrates the reduction of drug resistance in cancer cell lines by regulating the mitochondrial pH and depolarizing the mitochondrial membrane.