Molecular Imaging of Mucin-Expressing Colon tumors Using Targeted Hyperpolarized Silicon Nanoparticles
Liu, Julie Xinli
Constantinou Papadopoulos, Pamela; Carson, Daniel
Master of Arts
Colon cancer remains a leading cause of death due to limitations in clinical detection and prevention. Accordingly, an improved method with higher degree of detection sensitivity is due, where tumor surface markers can be targeted, and non-invasively imaged. MUC1 is a transmembrane mucin that is normally expressed only the apical aspect of colonic epithelia. MUC1 is a heavily glycosylated, large molecular weight protein that extends 200 to 500 nm above the cell surface. Accompanying cellular transformation and tumor development, MUC1 often becomes aberrantly expressed, including loss of polarized expression and altered glycosylation. With MUC1 as target, MUC1 antibody-functionalized silicon nanoparticles (SiNP may be used as uniquely hyperpolarizable imaging agents for the ultimate purpose of in vivo clinical applications for early colon tumor detection. This study aims to develop MUC1-targeting SiNPs that can undergo the hyperpolarization process to be utilized as sensitive image contrast agents to detect MUC1-expressing tumors. With cancer-associated transmembrane mucins found in most GI tract cancers, this silicon nanoparticle-based tumor diagnostic approach offers the potential to be expanded to detect tumors of other GI tissues and organs and establishes the basis for using other surface markers as detection targets.
APDMES (3-aminopropyl)-dimethyl-ethoxysilane; APTES (3-Aminopropyl)triethoxysilane; BME β-Mercaptoethanol; BSA bovine serum albumin; CRC Colorectal cancer; More... DAPI 4',6-diamidino-2-phenylindole; DMEM Dulbecco's Modified Eagle Medium; DMSO Dimethyl sulfoxide; FBS Fetal bovine serum; HBSS Hanks balanced salt solution; HEPES 4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid; MRI magnetic resonance imaging; NEAA non-essential amino acid; NHS N-hydrozysuccinimide; PBS Phosphate-buffered saline; PBST Phosphate-buffered saline with 0.1% (v/v) Tween-20; PEG Polyethylene glycol; RPMI Roswell Park Memorial Institute medium; SiP Silicon particle; SiNP Silicon nanoparticle; TCEP Tris(2-carboxyethyl1)phosphine Less...