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 bioinspired silification strategy is developed to prepare Fe3O4@SiO2 nanoparticles, instrinsically being covered by a layer of free poly(ethylene oxide) (PEO) chains on the surface. The resultant nanoparticles are highly stable not only in aqueous environment, but also in the presence of proteins under physiological conditions. These nanoparticles exhibit high transverse (r2) and low longitudinal (r1) relaxivities, making them efficient magnetic resonance contrast agents.
Ligand-mediated magnetic resonance (MR) contrast agents would be highly desirable for cancer diagnosis. In the present study, nanoparticles of Fe3O4 core with fluorescent SiO2 shell were synthesized ...and grafted with hyperbranched polyglycerol (HPG-grafted Fe3O4@SiO2 nanoparticles). These nanoparticles have a hydrodynamic diameter of 47.0 ± 4.0 nm, and are very stable in aqueous solution as well as in cell culture medium. Numerous surface hydroxyl groups of these nanoparticles were conjugated with folic acid by a thiol ‘click’ reaction. The successful covalent attachment of folic acid on the nanoparticles was confirmed by FTIR and XPS analyses. Both MR imaging and fluorescence microscopy show significant preferential uptake of the folic acid-conjugated polyglycerol-grafted Fe3O4@SiO2 (FA-HPG-grafted Fe3O4@SiO2) nanoparticles by human ovarian carcinoma cells (SKOV-3) as compared to macrophages and fibroblasts. Such nanoparticles can potentially be used to provide real-time imaging in ovarian cancer resection.
Background Clinical practice guidelines recommend using equations for estimating glomerular filtration rate (GFR) in chronic kidney disease (CKD) management and research. The MDRD (Modification of ...Diet in Renal Disease) Study and CKD-EPI (CKD Epidemiology Collaboration) equations originally were derived from a North American population and had an ethnic coefficient adjustment for African Americans. A Chinese coefficient for the MDRD Study equation subsequently was determined, but this has not been externally validated. We compared the accuracy of the equations, evaluated the ethnic coefficients, and assessed the equations for disease staging in a multiethnic Asian population with CKD. Study Design A diagnostic test study comparing the Asian coefficient (and subgroups)–modified MDRD Study and CKD-EPI equations and a cross-sectional study assessing disease staging. Setting & Participants 232 outpatients (52% men; 40.5% Chinese, 32% Malay, and 27.5% Indian/other) with stable CKD. Index Test Asian and ethnicity-based modifications of the MDRD Study and CKD-EPI equations. Reference Test Measured GFR using 3-sample plasma clearance of technetium-99m diethylenetriaminepentaacetic acid (99m Tc-DTPA), calculated using the slope-intercept method, with body surface area normalization (du Bois) and Brochner-Mortensen correction. Results Overall, the CKD-EPI equation is more accurate than the MDRD Study equation throughout the GFR range, with improved bias (median difference of estimated GFR − measured GFR) and root mean square error ( P <0.001). CKD-EPI versus MDRD Study equation: bias, 1.1 ± 13.8 vs −1.0 ± 15.2 mL/min/1.73 m2 ; precision, 12.1 vs 12.2 mL/min/1.73 m2 . Ethnic coefficients did not improve estimates of GFR significantly. The correctness of staging was improved using the CKD-EPI equation. Limitations All participants had CKD, but few were of European descent. The reference GFR technique was different from the original studies. Conclusions The CKD-EPI is more accurate than the MDRD Study equation, particularly at higher GFRs. Therefore, we recommend adopting the CKD-EPI equation without ethnic adjustment for estimating GFR in multiethnic Asian patients with CKD.
Selective internal radiotherapy (SIRT) with yttrium-90 ((90)Y) resin microspheres can improve the clinical outcomes for selected patients with inoperable liver cancer. This technique involves ...intra-arterial delivery of β-emitting microspheres into hepatocellular carcinomas or liver metastases while sparing uninvolved structures. Its unique mode of action, including both (90)Y brachytherapy and embolization of neoplastic microvasculature, necessitates activity planning methods specific to SIRT.
A panel of clinicians experienced in (90)Y resin microsphere SIRT was convened to integrate clinical experience with the published data to propose an activity planning pathway for radioembolization.
Accurate planning is essential to minimize potentially fatal sequelae such as radiation-induced liver disease while delivering tumoricidal (90)Y activity. Planning methods have included empiric dosing according to degree of tumor involvement, empiric dosing adjusted for the body surface area, and partition model calculations using Medical Internal Radiation Dose principles. It has been recommended that at least two of these methods be compared when calculating the microsphere activity for each patient.
Many factors inform (90)Y resin microsphere SIRT activity planning, including the therapeutic intent, tissue and vasculature imaging, tumor and uninvolved liver characteristics, previous therapies, and localization of the microsphere infusion. The influence of each of these factors has been discussed.
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.
Grafting hyperbranched polyglycerol (HPG) onto Fe3O4 nanoparticles results in novel superparamagnetic HPG‐grafted superparamagnetic nanoparticles that are highly stable and dispersible in aqueous medium. These magnetic nanoparticles (MNPs) have a high ratio of traverse to longitudinal relaxivities (r2/r1) and low macrophage uptake. Thus, they are potentially an excellent contrast agent for magnetic resonance imaging.
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.
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.
Superparamagnetic magnetite nanoparticles have been under intensive investigation in nanomedicine. However, it is still a challenge to synthesize high-quality water-stable magnetite nanoparticles for ...better magnetic performance and less side effects in medical MRI and nanothermotherapy.
We successfully synthesized hydrophilic magnetite nanoparticles through thermal decomposition of Fe(acac)(3) in triethylene glycol, which were coated with a triethylene glycol layer and thus demonstrated excellent water stability.
The optimized deposition temperature has been found to be 250°C (IO-250 NPs). The magnetic and thermal properties as well as the cytotoxicity of IO-250 NPs were investigated. In vitro experiments have demonstrated high cellular uptake and low cytotoxicity. The hyperthermia experiments showed effectiveness in temperature rise and cancer cell death. IO-250 NPs showed promising MRI with relaxivity r(2)* as high as 617.5 s(-1) mM(-1) Fe. In vivo MRI showed excellent tumor imaging.
The IO-250 NPs have great potential to be applied for clinical MRI and magnetic thermotherapy.
It is imperative that users of voxel-based morphometry (VBM) be aware of its reproducibility and the factors which influence results. We assessed the reproducibility of a VBM software package (SPM5) ...in measuring gray matter (GM) and white matter (WM) volumes from at least two consecutive 3D T1-weighted studies in 64 subjects. Factors investigated were the inter-study interval (ISI: 2.2 h to 124 days), signal-to-noise ratio (SNR: number of image averages (NA)=1 or 2), scanner software version and idle time. SNR was measured by direct estimation of tissue noise (SNRTN) and mean intensity in noise-only voxels (SNRNO). After the scanner software upgrade, voxel intensity increased 5-fold and WM mean SNRTN by 24% (p<0.001). Mean WM and GM volume changes in consecutive studies were near 0% (absolute SD of 7 ml and 10 ml respectively). Studies acquired with original scanner software showed a small (1.6%) mean GM volume increase attributed to SNRTN increases in five subjects due to scanner maintenance. GM volumes increased with SNRTN across the software upgrade (up to 4.3%; p<0.01) and NA=2 acquisitions (up to 4.1%; p<0.001). GM and WM volumes were independent of ISI when ISI did not encompass the software change. Scanner idle times of >6 h decreased SNR by 7% (p<0.001). SPM5 failed to include visible peripheral GM in only 2 subjects. SNRTN increases were greater than SNRNO increases across the software upgrade. It was concluded that SNR changes significantly influence SPM5-derived GM volumes. SNR may be influenced by scanner software upgrades and hardware condition and should be routinely assessed in studies of brain volume.
To date, few studies have examined the functional connectivity of brain regions involved in complex executive function tasks, such as cognitive set-shifting. In this study, eighteen healthy ...volunteers performed a cognitive set-shifting task modified from the Wisconsin card sort test while undergoing functional magnetic resonance imaging. These modifications allowed better disambiguation between cognitive processes and revealed several novel findings: 1) peak activation in the caudate nuclei in the first instance of negative feedback signaling a shift in rule, 2) lowest caudate activation once the rule had been identified, 3) peak hippocampal activation once the identity of the rule had been established, and 4) decreased hippocampal activation during the generation of new rule candidates. This pattern of activation across cognitive set-shifting events suggests that the caudate nuclei play a role in response generation when the identity of the new rule is unknown. In contrast, the reciprocal pattern of hippocampal activation suggests that the hippocampi help consolidate knowledge about the correct stimulus–stimulus associations, associations that become inappropriate once the rule has changed. Functional connectivity analysis using Granger Causality Mapping revealed that caudate and hippocampal regions interacted indirectly via a circuit involving the medial orbitofrontal and posterior cingulate regions, which are known to bias attention towards stimuli based on expectations built up from task-related feedback. Taken together, the evidence suggests that these medial regions may mediate striato-hippocampal interactions and hence affect goal-directed attentional transitions from a response strategy based on stimulus–reward heuristics (caudate-dependent) to one based on stimulus–stimulus associations (hippocampus-dependent).
