Investigating the uptake of mannose-conjugated ferritin by macrophages: effect of spacers

• Main Author: Lee, Mei Qin
• Other Authors: Sierin Lim
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2024
• Subjects: Chemistry; Engineering
• Online Access: https://hdl.handle.net/10356/178446
• Institution: Nanyang Technological University

Atherosclerosis is a chronic inflammatory disease which causes the narrowing of the artery and can lead to serious health consequences such as heart attacks and strokes. Hence, early detection of atherosclerosis is important for timely interventions. Macrophages play a critical role in atherosclerosis development and progression. Two major phenotypes of macrophages are seen to be present in atherosclerotic plaques, namely M1 (pro-inflammatory) and M2 (anti-inflammatory). M2 macrophages are more prevalent at the site of the plaques during the early stages of atherosclerosis and this study aims at targeted magnetic resonance imaging (MRI) of these M2 macrophages. MRI is an imaging modality that serves to detect and image atherosclerotic plaques. Ferritin nanocages have demonstrated their potential as MRI contrast agents. Since M2 macrophages express mannose receptors on their surface, ferritin conjugated with mannose can be used to target M2 macrophages for early-stage detection using MRI. However, ligand-receptor mediated uptake can be affected by the clustering of the ligands around the receptors on M2. The aim of this project is to study the effect of using poly(ethylene glycol) (PEG) spacers between ferritin and mannose on the uptake of mannose-PEG-ferritin by M2 macrophages. In the current study, the reaction for conjugation of PEG spacers to the surfaces of ferritin was optimized and then characterised. Conjugation protocols as described in this project could be further optimized for different conjugation requirements.