(619e) Surface Modifications of Iron Oxide Nanoparticle MRI Contrast Agents for Dual Targeting of Prostate Cancer

Individualized solutions for detecting cancer result in more accurate tumor diagnosis, less off target side effects, and improved patient outcomes. Currently, contrast enhanced Magnetic Resonance Imaging (MRI) is one of the most widely used cancer diagnostic techniques for its high resolution and noninvasive nature. Although various contrast agents with excellent magnetic properties have been approved for clinical use, they suffer from low biocompatibility and specificity. Our goal is to refine a series of surface modifications to enhance the safety and efficiency of an iron-based MRI contrast agent and achieve targeted imaging of tumors.

The presented work explores the optimization of an Iron Oxide Nanoparticle (IONP) contrast agent with a dual-targeted, PEGylated liposome coating and its effect on biocompatibility and specificity toward Prostate Cancer (PCa) in vitro. Using Fluorescence-Activated Cell Sorting (FACS), the folate receptor (FR) and prostate specific membrane antigen (PSMA) were identified as overexpressed biomarkers in many PCa cells for subsequent small molecule targeting. Conjugation of targeting ligands folic acid (FA) and DUPA are varied to analyze the effect of ligand grafting density on targeting efficiency. Cellular uptake and selectivity are measured using the ferrozine assay and magnetic hyperflux. PEG grafting density was also adjusted and quantified to determine the effect on targeting efficiency, cytotoxicity, and stability.

These investigations will give insight into the balance of multivalent targeting and PEGylation to achieve optimal targeting efficiency and biocompatibility. Designing individualized approaches to cancer diagnosis is part of the latest advancements in nanomedicine and will enhance the accuracy and reliability of diagnostic conclusions, improving resulting treatment plans. This work will help us better understand the most influential design parameters key to achieving safe and efficient targeted imaging of various tumors.