Synthesis of small-sized, porous, and low-toxic magnetite nanoparticles by thin POSS silica coating.

In this communication, we report the synthesis of small-sized (<10 nm), water-soluble, magnetic nanoparticles (MNPs) coated with polyhedral oligomeric silsesquioxanes (POSS), which contain either polyethylene glycol (PEG) or octa(tetramethylammonium) (OctaTMA) as functional groups. The POSS-coated MNPs exhibit superparamagnetic behavior with saturation magnetic moments (51-53 emu g(-1)) comparable to silica-coated MNPs. They also provide good colloidal stability at different pH and salt concentrations, and low cytotoxicity to MCF-7 human breast epithelial cells. The relaxivity data and magnetic resonance (MR) phantom images demonstrate the potential application of these MNPs in bioimaging.

Molecular Imaging Investigations of Polymer-Coated Cerium Oxide Nanoparticles as a Radioprotective Therapeutic Candidate.

Cerium oxide nanoparticles (CONPs) have a unique surface redox chemistry that appears to selectively protect normal tissues from radiation induced damage. Our prior research exploring the biocompatibility of polymer-coated CONPs found further study of poly-acrylic acid (PAA)-coated CONPs was warranted due to improved systemic biodistribution and rapid renal clearance. This work further explores PAA-CONPs' radioprotective efficacy and mechanism of action related to tumor microenvironment pH. An ex vivo TUNEL assay was used to measure PAA-CONPs' protection of the irradiated mouse colon in comparison to the established radioprotector amifostine. [18F]FDG PET imaging of spontaneous colon tumors was utilized to determine the effects of PAA-CONPs on tumor radiation response. In vivo MRI and an ex vivo clonogenic assay were used to determine pH effects on PAA-CONPs' radioprotection in irradiated tumor-bearing mice. PAA-CONPs showed excellent radioprotective efficacy in the normal colon that was equivalent to uncoated CONPs and amifostine. [18F]FDG PET imaging showed PAA-CONPs do not affect tumor response to radiation. Normalization of tumor pH allowed some radioprotection of tumors by PAA-CONPs, which may explain their lack of tumor radioprotection in the acidic tumor microenvironment. Overall, PAA-CONPs meet the criteria for clinical application as a radioprotective therapeutic agent and are an excellent candidate for further study.

Stronger brain activation for own baby but similar activation toward babies of own and different ethnicities in parents living in a multicultural environment.

Specific facial features in infants automatically elicit attention, affection, and nurturing behaviour of adults, known as the baby schema effect. There is also an innate tendency to categorize people into in-group and out-group members based on salient features such as ethnicity. Societies are becoming increasingly multi-cultural and multi-ethnic, and there are limited investigations into the underlying neural mechanism of the baby schema effect in a multi-ethnic context. Functional magnetic resonance imaging (fMRI) was used to examine parents' (N = 27) neural responses to (a) non-own ethnic in-group and out-group infants, (b) non-own in-group and own infants, and (c) non-own out-group and own infants. Parents showed similar brain activations, regardless of ethnicity and kinship, in regions associated with attention, reward processing, empathy, memory, goal-directed action planning, and social cognition. The same regions were activated to a higher degree when viewing the parents' own infant. These findings contribute further understanding to the dynamics of baby schema effect in an increasingly interconnected social world.

Brain-Computer Interfacing Using Functional Near-Infrared Spectroscopy (fNIRS).

Functional Near-Infrared Spectroscopy (fNIRS) is a wearable optical spectroscopy system originally developed for continuous and non-invasive monitoring of brain function by measuring blood oxygen concentration. Recent advancements in brain-computer interfacing allow us to control the neuron function of the brain by combining it with fNIRS to regulate cognitive function. In this review manuscript, we provide information regarding current advancement in fNIRS and how it provides advantages in developing brain-computer interfacing to enable neuron function. We also briefly discuss about how we can use this technology for further applications.

Amyloid Beta42 (Aß42) Peptide Functionalized Iron Oxide Nanoparticles for Specific Targeting of SH-SY5Y Neuroblastoma Cells.

One of the most severe diseases threatening the ageing population is Alzheimer's disease (AD). Recent studies found that the cellular uptake of extracellular amyloid beta (Aß) peptides can lead to a build-up of intracellular Aß in certain neuronal cells, which consequently lead to the onset of AD pathogenesis. It is therefore hypothesized that the detection of cells that are involved in such Aß uptake could facilitate the early diagnosis of AD. In this work, a magnetofluorescent nanoprobe was prepared conjugating dye-labeled Aß42 peptides with iron oxide nanoparticles (IONPs). When incubated with SH-SY5Y cells, the cellular uptake of Aß42-IONPs was enhanced, compared to that of bare IONPs. Further, by labelling SH-SY5Y and HCT-116 cells, it was found that the Aß42-IONPs are selectively targeting the neuronal cells. This enhanced and specific neuronal targeting is attributed to the cellular uptake of extracellular amyloid by SH-SY5Y cells. In addition, the MR relaxivities of the Aß42-IONPs are preserved after the peptides functionalization. The results suggest that the Aß42 functionalized magnetofluorescent IONPs can be used as a bimodal probe to interrogate the cellular uptake of amyloid peptides.

"Smart" theranostic lanthanide nanoprobes with simultaneous up-conversion fluorescence and tunable T1-T2 magnetic resonance imaging contrast and near-infrared activated photodynamic therapy.

The current work reports a type of "smart" lanthanide-based theranostic nanoprobe, NaDyF4:Yb(3+)/NaGdF4:Yb(3+),Er(3+), which is able to circumvent the up-converting poisoning effect of Dy(3+) ions to give efficient near infrared (980 nm) triggered up-conversion fluorescence, and offers not only excellent dark T2-weighted MR contrast but also tunable bright and T1-weighted MR contrast properties. Due to the efficient up-converted energy transfer from the nanocrystals to chlorin e6 (Ce6) photosensitizers loaded onto the nanocrystals, cytotoxic singlet oxygen was generated and photodynamic therapy was demonstrated. Therefore, the current multifunctional nanocrystals could be potentially useful in various image-guided diagnoses where bright or dark MRI contrast could be selectively tuned to optimize image quality, but also as an efficient and more penetrative near-infrared activated photodynamic therapy agent.

Silica-F127 nanohybrid-encapsulated manganese oxide nanoparticles for optimized T1 magnetic resonance relaxivity.

To properly engineer MnO nanoparticles (MONPs) of high r1 relaxivity, a nanohybrid coating consisting of silica and F127 (PEO106PPO70PEO106) is designed to encapsulate MONPs. Achieved by an interfacial templating scheme, the nanohybrid encapsulating layer is highly permeable and hydrophilic to allow for an optimal access of water molecules to the encapsulated manganese oxide core. Hence, the efficacy of MONPs as MRI contrast agents is significantly improved, as demonstrated by an enhancement of the MR signal measured with a pre-clinical 7.0 T MRI scanner. The nanohybrid encapsulation strategy also confers high colloidal stability to the hydrophobic MONPs by the surface decoration of PEO chains and a small overall diameter (<100 nm) of the PEO-SiO2 nanohybrid-encapsulated MONPs (PEOMSNs). The PEOMSNs are not susceptible to Mn-ion leaching, and their biocompatibility is affirmed by a low toxicity profile. Moreover, these hybrid nanocapsules exhibit a nano-rattle structure, which would favor the facile loading of various therapeutic reagents for theranostic applications.

Intrinsically radiolabelled [(59)Fe]-SPIONs for dual MRI/radionuclide detection.

Towards the development of iron oxide nanoparticles with intrinsically incorporated radionuclides for dual Positron Emission Tomography/Magnetic Resonance Imaging (PET/MRI) and more recently of Single Photon Emission Computed Tomography/Magnetic Resonance Imaging (SPECT/MRI), we have developed intrinsically radiolabeled [(59)Fe]-superparamagnetic iron oxide nanoparticles ([(59)Fe]-SPIONs) as a proof of concept for an intrinsic dual probe strategy. (59)Fe was incorporated into Fe3O4 nanoparticle crystal lattice with 92±3% efficiency in thermal decomposition synthesis. Multidentate poly(acrylic acid)-dopamine-poly(ethylene-glycol-2000) (PAA-DOP-PEG) ligands were designed and synthesized based on facile EDC chemistry and utilized to functionalize the [(59)Fe]-SPIONs. The transverse relaxivity of [(59)Fe]-SPIONs (97±3 s(-1)mM(-1)) was characterized and found to be similar to non-radioactive SPIONs (72±10 s(-1)mM(-1)), indicating that (59)Fe incorporation does not alter the SPIONs' MRI contrast properties. [(59)Fe]-SPIONs were used to evaluate the nanoparticle biodistribution by ex vivo gamma counting and MRI. Nude mice (n=15) were injected with [(59)Fe]-SPIONs and imaged at various time points with 7T small animal MRI scanner. Ex vivo biodistribution was evaluated by tissue-based gamma counting. MRI signal contrast qualitatively correlates with the %ID/g of [(59)Fe]-SPIONs, with high contrast in liver (45±6%), medium contrast in kidneys (21±5%), and low contrast in brain (4±6%) at 24 hours. This work demonstrates the synthesis and in vivo application of intrinsically radiolabeled [(59)Fe]-SPIONs for bimodal detection and provides a proof of concept for incorporation of both gamma- and positron-emitting inorganic radionuclides into the core of metal based MRI contrast agent nanoparticles.

A comparison of PET imaging agents for the assessment of therapy efficacy in a rodent model of glioma.

The aim of the current study was to assess the ability of PET imaging agents to detect early response to therapy in an orthotopic experimental rodent model of glioma. Clinically, MRI and [(18)F]FDG PET are routinely used but their ability to assess early therapeutic response can be limited. In this study, nude rats were implanted with U87-MG tumors orthotopically and imaged with either [(18)F]FDG or [(18)F]FLT to determine which tracer acts as the most sensitive biomarker for evaluation of treatment response in animals undergoing anti-angiogenic therapy with sunitinib, a receptor tyrosine kinase (RTK) inhibitor. Of the radiopharmaceuticals tested, [(18)F]FLT proved to be the most sensitive biomarker in the proliferating glioma, based on tumour-to-normal tissue radiotracer uptake (TNR ~17) in comparison to [(18)F]FDG (TNR ~1.7). Furthermore, [(18)F]FLT displayed earlier assessment of therapy efficacy, than either tumour volume measured by MRI or [(18)F]FDG PET imaging. Overall, longitudinal molecular imaging with [(18)F]FLT provides earlier detection of therapy response than either of the commonly used clinical imaging modalities potentially improving patient management.

Design and synthesis of polymer-functionalized NIR fluorescent dyes--magnetic nanoparticles for bioimaging.

The fluorescent probes having complete spectral separation between absorption and emission spectra (large Stokes shift) are highly useful for solar concentrators and bioimaging. In bioimaging application, NIR fluorescent dyes have a greater advantage in tissue penetration depth compared to visible-emitting organic dyes or inorganic quantum dots. Here we report the design, synthesis, and characterization of an amphiphilic polymer, poly(isobutylene-alt-maleic anhyride)-functionalized near-infrared (NIR) IR-820 dye and its conjugates with iron oxide (Fe3O4) magnetic nanoparticles (MNPs) for optical and magnetic resonance (MR) imaging. Our results demonstrate that the Stokes shift of unmodified dye can be tuned (from ~106 to 208 nm) by the functionalization of the dye with polymer and MNPs. The fabrication of bimodal probes involves (i) the synthesis of NIR fluorescent dye (IR-820 cyanine) functionalized with ethylenediamine linker in high yield, >90%, (ii) polymer conjugation to the functionalized NIR fluorescent dye, and (iii) grafting the polymer-conjugated dyes on iron oxide MNPs. The resulting uniform, small-sized (ca. 6 nm) NIR fluorescent dye-magnetic hybrid nanoparticles (NPs) exhibit a wider emissive range (800-1000 nm) and minimal cytotoxicity. Our preliminary studies demonstrate the potential utility of these NPs in bioimaging by means of direct labeling of cancerous HeLa cells via NIR fluorescence microscopy and good negative contrast enhancement in T2-weighted MR imaging of a murine model.

Tuning sub-10 nm single-phase NaMnF3 nanocrystals as ultrasensitive hosts for pure intense fluorescence and excellent T1 magnetic resonance imaging.

We report ultrasensitive sub-10 nm NaMnF(3) nanocrystals codoped with Yb(3+), Er(3+)/Tm(3+) ions, and their intense pure red and near-infrared upconversion emissions in the presence of Mn(2+). The nanocrystals showed excellent T(1) contrast in 7 T MRI, implying their potential as single-phase contrast agents for fluorescent deep tissue and MR imaging.