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Dual-mode nanoparticle probes for high-performance magnetic resonance and fluorescence imaging of neuroblastoma.

Inorganic nanoparticles are emerging as potential probes in next-generation biomedical applications. Their enhanced properties arising from nanoscale effects and their comparable size to biofunctional molecules have allowed for ultrasensitive detection of biomolecular targets. Of the various nanoparticles, quantum dots and fluorescent-dye-doped silica nanoparticles are representative examples of optical nanoprobe systems. Dye-doped silica nanoparticles have several advantages for optical imaging: 1) high photostability arising from the stabilization of dye molecules in a protective silica matrix, 2) amplification of the fluorescent signal owing to high dye-incorporation capabilities of silica nanoparticles, and 3) the silica is known to be relatively biocompatible and less toxic. On the other hand, magnetic nanoparticles exhibit a unique magnetic-resonance (MR) contrast enhancement effect that enables noninvasive MR imaging of cell trafficking, gene expression, and cancer. However, retrieving detailed biological information on a subcellular level is difficult owing to limited resolution and low sensitivity of the MRI technique. Until now, most previous studies that utilized optical and/or magnetic nanoparticle probes have been focused on monofunctional probes, except for a few primitive dual probes such as the single magnetic nanoparticle that was directly linked to organic dyes. Our strategy for the development of the next generation of nanoprobes has been to fuse multiple fluorescent dyes and multiple magnetic nanoparticles into a single nanoprobe that provides superior fluorescence and MR imaging capabilities through the synergistic enhancement of its respective components. Specifically, we have fabricated new “core–satellite” structured dual functional nanoparticles comprised of a dyedoped silica “core” and multiple “satellites” of magnetic nanoparticles. We further demonstrate their utilization as simultaneous optical and MR imaging of neuroblastoma cells expressing polysialic acids (PSAs). Detection of PSA is important as it is not only an important carbohydrate associated with neural pathways, such as synaptic plasticity, learning and memory, and cell-to-cell interaction, but it is also a marker of neuroblastoma, lung carcinoma, and Wilms7 tumors. Rhodamine-dye-doped silica (DySiO2) nanoparticles with surface amine groups were synthesized by a modified literature method. The obtained nanoparticles have a homogeneous size of 30 nm (Figure 1b). High-quality watersoluble iron oxide (Fe3O4, abbreviated as WSIO) nanoparticles were synthesized following a method previously reported by us. The WSIO nanoparticles are 9 nm in diameter with high monodispersity (s 5%) and coated with 2,3-dimercaptosuccinic acid (DMSA; Figure 1c). Our core–satellite nanoparticles were fabricated through the conjugation of these DySiO2 nanoparticles with WSIO by using sulfosuccinimidyl-(4-N-maleimidomethyl)cyclohexane1-carboxylate (sulfo-SMCC, Pierce) cross-linkers (Figure 1a). First, the amine groups of the DySiO2 nanoparticle were modified with maleimide groups by reacting them with sulfoSMCC cross-linkers. The reactions between the maleimide groups of the silica nanoparticle and the thiol groups ofWSIO nanoparticles subsequently yielded hybrid nanoparticles ((DySiO2–(Fe3O4)n, n= 10 2) of a dye-doped silica core and iron oxide satellites. [*] S.-I. Yeon, Prof. J.-S. Shin Department of Microbiology College of Medicine Yonsei University Seoul 120-752 (Korea) E-mail: jsshin6203@yumc.yonsei.ac.kr