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The biocompatibility and performance of reagents for in vivo contrast-enhanced magnetic resonance imaging (MRI) are essential for their translation to the clinic. The quality of the surface coating of nanoparticle-based MRI contrast agents, such as ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs), is critical to ensure high colloidal stability in biological environments, improved magnetic performance, and dispersion in circulatory fluids and tissues. Herein, we report the design of a library of 21 peptides and ligands and identify highly stable self-assembled monolayers on the USPIONs' surface. A total of 86 different peptide-coated USPIONs are prepared and selected using several stringent criteria, such as stability against electrolyte-induced aggregation in physiological conditions, prevention of nonspecific binding to cells, and absence of cellular toxicity and contrast-enhanced in vivo MRI. The bisphosphorylated peptide 2PG-S*VVVT-PEG4-ol provides the highest biocompatibility and performance for USPIONs, with no detectable toxicity or adhesion to live cells. The 2PG-S*VVVT-PEG4-ol-coated USPIONs show enhanced magnetic resonance properties, r (2.4 mM·s) and r (217.8 mM·s) relaxivities, and greater r/ r relaxivity ratios (>90) when compared to those of commercially available MRI contrast agents. Furthermore, we demonstrate the utility of 2PG-S*VVVT-PEG4-ol-coated USPIONs as a T contrast agent for in vivo MRI applications. High contrast enhancement of the liver is achieved as well as detection of liver tumors, with significant improvement of the contrast-to-noise ratio of tumor-to-liver contrast. It is envisaged that the reported peptide-coated USPIONs have the potential to allow for the specific targeting of tumors and hence early detection of cancer by MRI.

Stimuli-responsive nanoprobes that combine both fluorescence and magnetic resonance imaging (MRI) are anticipated to be highly beneficial for tumor visualization with high imaging sensitivity. By employing an interfacial templating scheme, a pH-activatable fluorescence/MRI dual-modality imaging nanoprobe is successfully developed based on the coencapsulation of MnO nanoparticles and coumarin-545T inside a hybrid silica nanoshell. To promote cancer cell targeting with high-specificity, the nanoprobes are also conjugated with folic acid to establish a greater affinity for cancer cells that over-express folate receptors on their cell membrane. In the new nanosystem, MnO nanoparticles are shown to function as an efficient fluorescence quencher of coumarin-545T prior to cellular uptake. However, fluorescence recovery is achieved upon acidic dissolution of the MnO nanoparticles following receptor-mediated endocytosis into the low pH compartments of the cancer cells. Meanwhile, the Mn(2+) ions thus released are also shown to exert a strong T1 contrast enhancement in the cancer cells. Therefore, by demonstrating the dual-activatable MRI and fluorescence imaging in response to the low pH conditions, it is envisioned that these nanoprobes would have tremendous potential for emerging cancer-imaging modalities such as image-guided cancer therapy.

wileyonlinelibrary.comA new hybrid nanoreactor framework with poly(ethylene oxide)-perforated silica walls is designed to encapsulate hollow manganese oxide nanoparticles (MONs) of high distinctness and homogeneity. Achieved by an interfacial templating scheme, the nanoreactor ensures that acidic etching of MONs by an acetate buffer solution is highly controlled for precise control of the hollow interior. As such, hollow MONs with different nanostructures are developed successfully through a facile acetate buffer solution etching. The resultant hollow MONs are integrated within the hybrid nanoreactor and demonstrate superior r 1 relativity of up to 2.58 m M −1 s −1 for T 1 magnetic resonance imaging (MRI). By modifying the nanoreactor architecture, it is also demonstrated that the effi cacy of MONs as T 1 MRI contrast agents can be signifi cantly improved if an optimal cluster of hollow MONs is encapsulated into the hybrid silica framework. The evolution of core morphology with time is studied to elucidate the etching mechanism. It is revealed that the hollow formation arises due to the surface stabilization of MONs by acetate ions and the subsequent acidic etching of the interior core in a sporadic manner. This is different from the commonly reported nanoscale Kirkendall effect or the selective etching of the core-shell MnO/Mn 3 O 4 structure.

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Background While regenerative stem cell therapy for ischemic heart disease has moved into phase 3 studies, little is still known about retention and migration of cell posttransplantation. In human studies, the ability to track transplanted cells has been limited to labeling with radioisotopes and tracking using nuclear imaging. This method is limited by low resolution and short half-lives of available radioisotopes. Longitudinal tracking using magnetic resonance imaging (MRI) of myocardial injected cells labeled with iron oxide nanoparticles has shown promising results in numerous preclinical studies but has yet to be evaluated in human studies. We aimed to evaluate MRI tracking of mesenchymal stromal cells (MSCs) labeled with ultrasmall paramagnetic iron oxide (USPIO) nanoparticles after intramyocardial transplantation in patients with ischemic heart disease (IHD). Methods Five no-option patients with chronic symptomatic IHD underwent NOGA-guided intramyocardial transplantation of USPIO-labeled MSCs. Serial MRI scans were performed to track labeled cells both visually and using semiautomated T2∗ relaxation time analysis. For safety, we followed symptoms, quality of life, and myocardial function for 6 months. Results USPIO-labeled MSCs were tracked for up to 14 days after transplantation at injection sites both visually and using semiautomated regional T2∗ relaxation time analysis. Labeling of MSCs did not impair long-term safety of treatment. Conclusion This was a first-in-man clinical experience aimed at evaluating the utility of MRI tracking of USPIO-labeled bone marrow-derived autologous MSCs after intramyocardial injection in patients with chronic IHD. The treatment was safe, and cells were detectable at injection sites up to 14 days after transplantation. Further studies are needed to clarify if MSCs migrate out of the injection area into other areas of the myocardium or if injected cells are washed out into the peripheral circulation. The trial is registered with ClinicalTrials.gov NCT03651791.

β-phase NaGdF4 nanocrystals doped with Er3+ and Yb3+ possessing diverse morphologies were synthesized from the thermolysis of trifluoroacetate precursors in 1-octadecene and oleic acid by modifying the hot-injection strategy. Modulation of the injection temperature during the hot-injection step was an effective approach to control the size and shape of the prepared nanocrystals and allowed for the direct synthesis of nanorods. Here, we report for the first time the fabrication of monodispersed uniform nanorods through a one-step thermolysis approach. The different supersaturation caused by the different temperatures could directly manipulate the nucleation and growth of α-phase nanoparticles before the α → β phase transition, subsequently influences the Ostwald ripening mode during the α → β phase transition, and consequently affects their morphology (i.e., nanorods, nanospheres, nanoprisms, nanoplates, and nanodisks), uniformity, and monodispersity. The upconversion luminescence intensity decreased with increase of the surface to volume ratio of the upconverting nanocrystals, and a higher ratio of green to red emission was observed when the aspect ratio was close to 1. The negative contrast enhancement on T 2-weighted magnetic resonance images caused by the upconverting nanocrystals was increased with increasing size with the exception of the nanorods, which performed the best as T 2 contrast agents despite being smaller compared to the nanoplates. Our work provided strong evidence for the use of morphology controlled synthesis in NaGdF4 based upconverting nanocrystals and their implementation in multifunctional nanoplatforms for future biomedical applications.

One-pot synthesis of theranostic nanocapsules with lanthanide doped nanoparticles via interfacial templating condensation for upconversion based photodynamic therapy.