Fluorescent magnetic nanoparticles with specific targeting functions for combinded targeting, optical imaging and magnetic resonance imaging

摘要

Superparamagnetic iron oxides nanoparticles possess specific magnetic properties to be an efficient contrast agent for magnetic resonance imaging (MRI) to enhance the detection and characterization of tissue lesions within the body. To endow specific properties to nanoparticles that can target cancer cells and prevent recognition by the reticuloendothelial system (RES), the surface of the nanoparticles was modified with folic-acid-conjugated poly(ethylene glycol) (FA-PEG). In this study, we investigated the multifunctional fluorescent magnetic nanoparticles (IOPFC) that can specifically target cancer cells and be monitored by both MRI and optical imaging. IOPFC consists of an iron oxide superparamagnetic nanoparticle conjugated with a layer of PEG, which was terminal modified with either Cypher5E or folic acid molecules. The core sizes of IOPFC nanoparticles are around 10 nm, which were visualized by transmission electron microscope (TEM). The hysteresis curves, generated with superconducting quantum interference device (SQUID) magnetometer analysis, demonstrated that IOPFC nanoparticles are superparamagnetic with insignificant hysteresis. IOPFC displays higher intracellular uptake into KB and MDA-MB-231 cells due to the over-expressed folate receptor. This result is confirmed by laser confocal scanning microscopy (LCSM) and atomic flow cytometry. Both in vitro and in vivo MRI studies show better IOPFC uptake by the KB cells (folate positive) than the HT1080 cells (folate negative) and, hence, stronger T _2-weighted signals enhancement. The in vivo fluorescent image recorded at 20 min post injection show strong fluorescence from IOPFC which can be observed around the tumor region. This multifunctional nanoparticle can assess the potential application of developing a magnetic nanoparticle system that combines tumor targeting, as well as MRI and optical imaging.