Convenient and effective ICGylation of magnetic nanoparticles for biomedical applications

Hye Sun Park,Jongwoo Kim,Sang Hwan Nam,Kwan Soo Hong,Hyunseung Lee,Mi Young Cho,Yung Doug Suh

doi:10.1038/s41598-017-09627-x

Abstract

Nanoprobes used for biomedical applications usually require surface modifications with amphiphilic surfactants or inorganic coating materials to enhance their biocompatibility. We proposed a facile synthetic approach for the phase transfer of hydrophobic magnetic nanoparticles by the direct adherence of fluorescent probes, without any chemical modifications, for use as a magnetic resonance (MR)/near-infrared (NIR) fluorescence bimodal imaging contrast agent. Indocyanine green (ICG) was used not only as an optical component for NIR imaging, but also as a surfactant for phase transfer with no superfluous moiety: we therefore called the process “ICGylation”. Cell labeling and tracking in vivo with ICGylated magnetic nanoparticles were successfully performed by MR/NIR dual-mode imaging for three days, which showed remarkable biostability without any additional surface functionalization. We expect that this novel MR/NIR contrast agent demonstrating sensitive detection and simultaneous imaging capability can be used in diverse fields, such as the imaging and tracking of immune cells to confirm immunotherapeutic efficacy. The approach used could also be applied to other kinds of nanoparticles, and it would promote the development of advanced functional multimodal nanobioprobes.

Highlights

Magnetic nanoparticles (MNPs) have been used in various fields[1] such as those involving magnetic resonance imaging (MRI)[2], biomedicine[3], catalysts[4], and data storage[5]
MNPs were synthesized by a two-step thermal decomposition procedure[37] and were observed by high-resolution transmission electron microscopy (HRTEM) images (Fig. 2a) to exhibit a uniform size distribution with a diameter of around 13.7 nm
indocyanine green (ICG) was coated onto the surface of MNPs using a single emulsion evaporation method wherein ICG molecules were dissolved in water and MNPs were dispersed in an organic phase: we termed this process ICGylation of MNPs

Summary

Results and Discussion

Fluorescence images were obtained for the same individual mouse (Fig. 5c), which showed clear detection of the left popliteal lymph nodes by NIR fluorescence signals These results were in accordance with in vivo MR imaging results, indicating that in vivo tracking of DCs via MR and fluorescence dual-mode imaging can be evaluated by labeling with ICGylated MNPs. Contrast-to-noise ratio (CNR) of each day indicates signal decrease in the lymph node over time (Fig. 5d), which was due to degradation of ICG molecules in the in vivo experiments. The migration of the labeled DCs via lymphatic drainage and homing into lymph nodes was monitored by real-time MR/NIR imaging for three days We expect that this novel MR/NIR contrast agent with sensitive detection and simultaneous imaging capabilities can be used in various fields, such as the imaging and tracking of immune cells to confirm immunotherapeutic efficacy. This principle can be applied to the phase transfer of other kinds of hydrophobic particles using amphiphilic fluorescent dyes to develop multimodal probes for biomedical applications

Methods

Author Contributions

Additional Information