Large-scale one-pot synthesis of water-soluble and biocompatible upconversion nanoparticles for dual-modal imaging.

Lanthanide-doped upconversion nanoparticles (UCNPs) have attracted considerable attentions in the area of molecular imaging, targeted therapy and diagnosis. The UCNPs synthesized by conventional methods are usually hydrophobic and require additional surface modification to give them water solubility and biocompatibility. Herein, we designed a simple and convenient strategy for the direct synthesis of water-soluble and biocompatible lanthanum-doped UCNPs through a one-pot reaction without further purification and screening. The doping amount of lanthanide can be adjusted by simply changing the proportion of precursor in the reaction solution. The resulting water-soluble UCNPs possess excellent colloidal stability in physiological media. Under 980 nm excitation, NaGdF4:Yb3+/Er3+ and NaGdF4:Yb3+/Tm3+ nanoparticles exhibited a dominant green emission band (4S3/2→4I15/2) of Er3+ and a dominant blue emission band (1G4→3H6) of Tm3+, respectively. Toxic response was not observed with concentration up to 50 mg/L. The hemolysis to rabbit red blood cells was less than 2% in the concentration up to 20 mg/L. The NaGdF4:Yb3+/Er3+ nanoparticles exhibited a high r1 relaxivity of 4.7 mM-1s-1, demonstrating that the water-soluble and biocompatible UCNPs can be efficient T1 contrast agents. The in vivo results show that UCNPs exhibit excellent T1-weighted imaging and fluorescence imaging abilities simultaneously, and can be used as a versatile promising theranostic nanoplatform.

Controllable synthesis of exceptionally small-sized superparamagnetic magnetite nanoparticles for ultrasensitive MR imaging and angiography.

The superparamagnetic magnetite nanoparticles have broad application prospects in the diagnosis and treatment of cancer. Herein, a series of monodispersed exceptionally small-sized superparamagnetic magnetite nanoparticles (ESM NPs) with tunable size were synthesized through thermal decomposition of an iron precursor by simply changing the reaction temperature and stabilizing agents. The underlying mechanisms of regulating the size and properties of ESM NPs were studied. The surface of hydrophobic ESM NPs was modified with a carboxyl-polyethylene glycol-phosphoric acid ligand, and the obtained water-soluble ESM NPs showed extremely high long-term stability under various aqueous environments and physiological conditions. The hemolysis and cytotoxicity evaluations showed that the ESM NPs had good blood compatibility and no obvious cytotoxicity. The 2.3 nm ESM NPs exhibited an extremely high longitudinal relaxivity (r1) of 6.0 mM-1 s-1, which was higher than that of the clinical gadolinium complex contrast agent (r1 = 3.8 mM-1 s-1), and had an appropriate r2/r1 ratio of 4.0. The in vivo results showed that the nanoparticles exhibited superior contrast effects in both T1 and T2 MR imaging, as well as high-resolution contrast in MR angiography. This study provides a general strategy for the controlled synthesis of ESM NPs and reveals the size and property regulation mechanisms, which undoubtedly provides the possibility of designing highly sensitive MR imaging probes based on small-sized magnetic nanoparticles for clinical diagnostic applications.

One-pot synthesis of water-soluble and biocompatible superparamagnetic gadolinium-doped iron oxide nanoclusters.

The synthesis of superparamagnetic nanoclusters is critical for ultra-sensitive magnetic resonance imaging (MRI). Herein, we describe the synthesis of water-soluble, biocompatible and superparamagnetic gadolinium-doped iron oxide nanoclusters (GdIO NCs) via a one-pot reaction by thermal decomposition of ferric oleate and gadolinium oleate precursors with α,ω-dicarboxyl poly(ethylene glycol) as a surfactant. The resulting water-dispersible GdIO NCs possess good stability and monodispersity with narrow size distribution, and exhibit superparamagnetic behaviors. We also explored the effect of gadolinium doping amounts on the magnetic properties and longitudinal (r1) and transverse relaxivity (r2) of the nanoclusters. In addition, the GdIO NCs can be functionalized with fluorescein isothiocyanate (FITC) while maintaining their magnetic properties and biocompatibility. The GdIO NCs and FITC conjugated NCs were preliminarily evaluated as MRI and fluorescent probes. The results show that the GdIO NCs provide an important nano-platform for theranostics with non-invasive MRI and optical monitoring capabilities.

Hydroxyl-PEG-Phosphonic Acid-Stabilized Superparamagnetic Manganese Oxide-Doped Iron Oxide Nanoparticles with Synergistic Effects for Dual-Mode MR Imaging.

The T1-T2 dual-mode contrast agents for magnetic resonance imaging (MRI) can generate self-complementary confirmed T2 and T1 images, hence greatly improving the reliability. Facilely synthesizing nanoparticles with the ultrasensitive contrast property remains extremely challenging in nanoscience. Moreover, uncovering the mechanism correlating the signal enhancements and chemical constituents is vital for designing novel efficient synergistically enhanced T1-T2 dual-mode MRI nanoprobes. Herein, we report a one-pot facile method to synthesize the superparamagnetic manganese oxide-doped iron oxide (Fe3O4/MnO) nanoparticles for T1-T2 dual-mode MR imaging. Under external magnetic field, the local magnetic field intensities of MnO and Fe3O4 could be simultaneously enhanced through embedding MnO into Fe3O4 nanoparticles and hence can cause synergistic T1 and T2 contrast enhancements. Moreover, a novel and facile cost-effective method for large-scale synthesis of hydroxyl-polyethylene glycol-phosphonic acid-stabilizing ligands is designed. The facile synthetic method and surface coating strategy of superparamagnetic Fe3O4/MnO nanoparticles offer an idea for the chemical design and preparation of superparamagnetic nanoparticles with ultrasensitive MRI contrast abilities for disease evaluation and treatment.