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In the present study, quantum dot (QD) capped magnetite nanorings (NRs) with a high luminescence and magnetic vortex core have been successfully developed as a new class of magnetic-fluorescent nanoprobe. Through electrostatic interaction, cationic polyethylenimine (PEI) capped QD have been firmly graft into negatively charged magnetite NRs modified with citric acid on the surface. The obtained biocompatible multicolor QD capped magnetite NRs exhibit a much stronger magnetic resonance (MR) T2* effect where the r2* relaxivity and r2*/r1 ratio are 4 times and 110 times respectively larger than those of a commercial superparamagnetic iron oxide. The multiphoton fluorescence imaging and cell uptake of QD capped magnetite NRs are also demonstrated using MGH bladder cancer cells. In particular, these QD capped magnetite NRs can escape from endosomes and be released into the cytoplasm. The obtained results from these exploratory experiments suggest that the cell-penetrating QD capped magnetite NRs could be an excellent dual-modality nanoprobe for intracellular imaging and therapeutic applications. This work has shown great potential of the magnetic vortex core based multifunctional nanoparticle as a high performance nanoprobe for biomedical applications.

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Inspired by the biosilification process, a highly benign synthesis strategy is successfully developed to synthesize PEOlated Fe3O4@SiO2 nanoparticles (PEOFSN) at room temperature and near‐neutral pH. The success of such a strategy lies in the simultaneous encapsulation of Fe3O4 nanocrystals and silica precursors into the core of PEO‐based polymeric micelles. The encapsulation results in the formation of a silica shell being confined to the interface between the core and corona of the Fe3O4‐nanocrystal‐loaded polymeric micelles. Consequently, the surface of the Fe3O4@SiO2 nanoparticle is intrinsically covered by a layer of free PEO chains, which enable the PEOFSN to be colloidally stable not only at room temperature, but also upon incubation in the presence of proteins under physiological conditions. In addition, the silica shell formation does not cause any detrimental effects to the encapsulated Fe3O4 nanocrystals with respect to their size, morphology, crystallinity, and magnetic properties, as shown by their physicochemical behavior. The PEOFSN are shown to be good candidates for magnetic resonance imaging (MRI) contrast agents as demonstrated by the high r2/r1 ratio with long‐term stability under high magnetic field, as well as the lack of cytotoxicity.

A system of poly(lactide‐co‐glycolide)‐methoxy poly(ethylene glycol) (PLGA‐mPEG) nanoparticles is developed to formulate superparamagnetic iron oxides (IOs) for magnetic resonance imaging (MRI). This system improves the imaging effects, increases the half‐life of the IOs in circulation, and reduces their side effects. The IO‐loaded PLGA‐mPEG nanoparticles were prepared by a modified water‐in‐oil‐in‐water double‐emulsion technique. Their physicochemical and superparamagnetic properties were characterized by various techniques. In vitro IO release kinetics from the nanoparticles and stability of the IO‐loaded polymeric nanoparticles were also investigated. In vitro and ex vivo MRI of the IOs formulated in the PLGA‐mPEG nanoparticles show that the saturation magnetization and the r2, r2* relaxivities are enhanced, and the contrast effects are improved in comparison with commercial IOs (Resovist). It is proven that the enhanced superparamagnetic properties are caused by the polymeric nanoparticle formulation but not by the polymeric material itself. Moreover, the PLGA‐mPEG nanoparticle formulation achieves 36.9 and 35.6 % less cytotoxicity in comparison with the IOs (Resovist) after 48 h incubation at the same 20 and 50 μg mL–1 Fe concentration, respectively. This research implies that formulation of IOs by nanoparticles of PLGA‐mPEG copolymer or other biodegradable polymers could be promising for more effective and sustainable MRI with reduced side effects, which, with targeting probes conjugated to the nanoparticle surface, can be further used to promote cellular and molecular MRI.

Hyperbranched polyglycerol‐grafted, magnetic Fe3O4 nanoparticles (HPG‐grafted MNPs) are successfully synthesized by surface‐initiated ring‐opening multibranching polymerization of glycidol. Reactive hydroxyl groups are immobilized on the surface of 6–9 nm Fe3O4 nanoparticles via effective ligand exchange of oleic acid with 6‐hydroxy caproic acid. The surface hydroxyl groups are treated with aluminum isopropoxide to form the nanosized macroinitiators. The successful grafting of HPG onto the nanoparticles is confirmed by infrared and X‐ray photoelectron spectroscopy. The HPG‐grafted MNPs have a uniform hydrodynamic diameter of (24.0 ± 3.0) nm, and are very stable in aqueous solution, as well as in cell culture medium, for months. These nanoparticles have great potential for application as a new magnetic resonance imaging contrast agent, as evidenced by their lack of cytotoxicity towards mammalian cells, low uptake by macrophages, excellent stability in aqueous medium and magnetic fields, and favorable magnetic properties. Furthermore, the possibility of functionalizing the hydroxyl end‐groups of the HPG with cell‐specific targeting ligands will expand the range of applications of these MNPs.

Magnetic resonance imaging (MRI) is emerging as a powerful tool for in vivo noninvasive tracking of magnetically labeled stem cells. In this work, we present an efficient cell-labeling approach using (carboxymethyl)chitosan-modified superparamagnetic iron oxide nanoparticles (CMCS-SPIONs) as contrast agent in MRI. The CMCS-SPIONs were prepared by conjugating (carboxymethyl)chitosan to (3-aminopropyl)trimethoxysilane-treated SPIONs. These nanoparticles were internalized into human mesenchymal stem cells (hMSCs) via endocytosis as confirmed by Prussian Blue staining and electron microscopy investigation and quantified by inductively coupled plasma mass spectrometry. A MTT assay of the labeled cells showed that CMCS-SPIONs did not possess significant cytotoxicity. In addition, the osteogenic and adipogenic differentiations of the hMSCs were not influenced by the labeling process. The in vitro detection threshold of cells after incubation with 0.05 mg/mL of CMCS-SPIONs for 24 h was estimated to be about 40 cells. The results from this study indicate that the biocompatible CMCS-SPIONs show promise for use with MRI in visualizing hMSCs.

Stem cell transplantation for regenerative medicine has made significant progress in various injury models, with the development of modalities to track stem cell fate and migration post-transplantation being currently pursued rigorously. Magnetic resonance imaging (MRI) allows serial high-resolution in vivo detection of transplanted stem cells labeled with iron oxide particles, but has been hampered by low labeling efficiencies. Here, we describe the use of microgel iron oxide (MGIO) particles of diameters spanning 100-750 nm for labeling human fetal mesenchymal stem cells (hfMSCs) for MRI tracking. We found that MGIO particle uptake by hfMSCs was size dependent, with 600-nm MGIO (M600) particles demonstrating threeto sixfold higher iron loading than the clinical particle ferucarbotran (33-263 versus 9.6-42.0 pg iron/hfMSC; p < .001). Cell labeling with either M600 particles or ferucarbotran did not affect either cellular proliferation or trilineage differentiation into osteoblasts, adipocytes, and chondrocytes, despite differences in gene expression on a genome-wide microarray analysis. Cell tracking in a rat photothrombotic stroke model using a clinical 1.5-T MRI scanner demonstrated the migration of labeled hfMSCs from the contralateral cortex to the stroke injury, with M600 particles achieving a five-to sevenfold higher sensitivity for MRI detection than ferucarbotran (p < .05). However, model-related cellular necrosis and acute inflammation limited the survival of hfMSCs beyond 5-12 days. The use of M600 particles allowed high detection sensitivity with low cellular toxicity to be achieved through a simple incubation protocol, and may thus be useful for cellular tracking using standard clinical MRI scanners.