An Atomic Insight into the Confusion on the Activity of Fe3O4 Nanoparticles as Peroxidase Mimetics and Their Comparison with Horseradish Peroxidase.

Although Fe3O4 nanoparticles were early reported to outperform horseradish peroxidase (HRP), recent studies suggested that this material bears a very poor activity instead. Here, we resolve this disagreement by reviewing the definition of descriptors used and provide an atomic view into the origin of Fe3O4 nanoparticles as peroxidase mimetics. The redox between H2O2 and Fe(II) sites on the Fe3O4 surface was identified as the key step to producing OH radicals for the oxidation of colorimetric substrates. This mechanism involving free radicals is distinct from that of HRP oxidizing substrates with a radical retained on its Fe-porphyrin ring. Surprisingly, the distribution and chemical state of Fe species were found to be very different on single- and polycrystalline Fe3O4 nanoparticles with the latter bearing not only a higher Fe(II)/Fe(III) ratio but also a more reactive Fe(II) species at surface grain boundaries. This accounts for the unexpected gap in the catalytic constant (kcat) observed for this material in the literature.

Low-toxicity FePt nanoparticles for the targeted and enhanced diagnosis of breast tumors using few centimeters deep whole-body photoacoustic imaging.

A considerable amount of early breast tumors grown at a depth over 2 cm in breast tissues. With high near-infrared absorption of iron-platinum (FePt) nanoparticles, we achieved few centimeters deep photoacoustic (PA) imaging for the diagnosis of breast tumors. The imaging depth can extend over 5 cm in chicken breast tissues at the low laser energy density of 20 mJ/cm2 (≤ ANSI safety limit). After anti-VEGFR conjugation and the tail-vein injection, we validated their targeting on tumor sites by the confocal microscopy and PA imaging. Using a home-made whole-body in vivo PA imaging, we found that the nanoparticles were rapidly cleared away from the site of the tumor and majorly metabolized through the liver. These results validated the clinical potential of the FePt nanoparticles in the low-toxicity PA theragnosis of early breast cancer and showed the capacity of our whole-body PA imaging technique on monitoring the dynamic biodistribution of nanoparticles in the living body.

Engineered core-shell magnetic nanoparticle for MR dual-modal tracking and safe magnetic manipulation of ependymal cells in live rodents.

Tagging recognition group(s) on superparamagnetic iron oxide is known to aid localisation (imaging), stimulation and separation of biological entities using magnetic resonance imaging (MRI) and magnetic agitation/separation (MAS) techniques. Despite the wide applicability of iron oxide nanoparticles in T 2-weighted MRI and MAS, the quality of the images and safe manipulation of the exceptionally delicate neural cells in a live brain are currently the key challenges. Here, we demonstrate the engineered manganese oxide clusters-iron oxide core-shell nanoparticle as an MR dual-modal contrast agent for neural stem cells (NSCs) imaging and magnetic manipulation in live rodents. As a result, using this engineered nanoparticle and associated technologies, identification, stimulation and transportation of labelled potentially multipotent NSCs from a specific location of a live brain to another by magnetic means for self-healing therapy can therefore be made possible.

A Versatile Theranostic Delivery Platform Integrating Magnetic Resonance Imaging/Computed Tomography, pH/cis-Diol Controlled Release, and Targeted Therapy.

The functions of biomedical imaging, cancer targeting, and controlled release of therapeutic agents were integrated into a drug delivery platform to proof its diagnostic and therapeutic capabilities. This versatile nanocomposite is based on the strategic design of wormlike mesoporous silica nanocarriers that are decorated with extremely small iron oxide nanoparticles, having a prominent T1-weighted Magnetic Resonance Imaging (MRI) signal. The controlled release function was then achieved through the grafting of polyalcohol saccharide derivative ligands onto the surfaces of mesoporous silica nanoparticles to conjugate with boronic acid functionalized gold nanoparticles, which acted as the gate and the source of computed tomography (CT) signals. This versatile platform thus exhibited a MRI/CT dual imaging property drawing on the strong points to offset the weaknesses of each, rendering more accurate diagnosis. The capping of gold nanoparticles controlled with the hydrolysis of boronate ester bonds provides the reversible opening/closing process, avoiding further release of drug once the nanocomposite leaves the cell or tissue. To endow this platform with targeting ability, protocatechuic acid was utilized as a linker to connect folic acid with the boronic acid of the gold nanoparticles. The anchor of targeting moiety, folic acid, enriched this platform and enhanced the specific cellular uptake toward cells with folate receptor. This integrated drug delivery platform was then loaded with the antitumor agent doxorubicin, demonstrating its power for targeted delivery, bioimaging, and controlled release chemotherapy to reduce the undesired side effects of chemotherapy.

Infrared-active quadruple contrast FePt nanoparticles for multiple scale molecular imaging.

A single nanomaterial with multiple imaging contrasts and functions is highly desired for multiscale theragnosis. Herein, we demonstrate single 1-1.9 µm infrared-active FePt alloy nanoparticles (FePt NPs) offering unprecedented four-contrast-in-one molecular imaging - computed tomography (CT), magnetic resonance imaging (MRI), photoacoustic (PA) imaging, and high-order multiphoton luminescence (HOMPL) microscopy. The PA response of FePt NPs outperforms that of infrared-active gold nanorods by 3- to 5.6-fold under identical excitation fluence and particle concentrations. HOMPL (680 nm) of an isolated FePt NP renders spatial full-width-at-half-maximum values of 432 nm and 300 nm beyond the optical diffraction limit for 1230-nm and 920-nm excitation, respectively. The in vivo targeting function was successfully visualized using HOMPL, PA imaging, CT, and MRI, thereby validating FePt as a single nanomaterial system covering up to four types (Optical/PA/CT/MRI) of molecular imaging contrast, ranging from the microscopic level to whole-body scale investigation.

One-step synthesis of degradable T(1)-FeOOH functionalized hollow mesoporous silica nanocomposites from mesoporous silica spheres.

The combination of a hollow mesoporous structure and a magnetic resonance (MR) contrast agent has shown its potential in simultaneous drug delivery and cell tracking applications. However, the preparation of this kind of nanocomposite is complicated and usually takes several days, which is unsuitable for scaled-up production. To overcome these hurdles, we report herein a facile method to synthesize iron oxide hydroxide functionalized hollow mesoporous silica spheres (FeOOH/HMSS) in a one-step manner. By carefully controlling the reaction kinetics of K2FeO4 in water, the gram-scale production of FeOOH/HMSS can be readily achieved at 60 °C for as short as 30 min. Most importantly, this synthetic process is also cost-effective and eco-friendly in both the precursor (K2FeO4 and H2O) and the product (FeOOH). The mechanism for the formation of a hollow structure was carefully investigated, which involves the synergetic effect of the surfactant CTAB and the side product KOH. Having outstanding biocompatibility, these degradable nanocolloids also demonstrate their feasibility in in vitro/vivo MR imaging and in vitro drug delivery.

One-step, room-temperature synthesis of glutathione-capped iron-oxide nanoparticles and their application in in vivo T1-weighted magnetic resonance imaging.

The room-temperature, aqueous-phase synthesis of iron-oxide nanoparticles (IO NPs) with glutathione (GSH) is reported. The simple, one-step reduction involves GSH as a capping agent and tetrakis(hydroxymethyl)phosphonium chloride (THPC) as the reducing agent; GSH is an anti-oxidant that is abundant in the human body while THPC is commonly used in the synthesis of noble-metal clusters. Due to their low magnetization and good water-dispersibility, the resulting GSH-IO NPs, which are 3.72 ± 0.12 nm in diameter, exhibit a low r2 relaxivity (8.28 mm(-1) s(-1)) and r2/r1 ratio (2.28)--both of which are critical for T1 contrast agents. This, together with the excellent biocompatibility, makes these NPs an ideal candidate to be a T1 contrast agent. Its capability in cellular imaging is illustrated by the high signal intensity in the T1-weighted magnetic resonance imaging (MRI) of treated HeLa cells. Surprisingly, the GSH-IO NPs escape ingestion by the hepatic reticuloendothelial system, enabling strong vascular enhancement at the internal carotid artery and superior sagittal sinus, where detection of the thrombus is critical for diagnosing a stroke. Moreover, serial T1- and T2-weighted time-dependent MR images are resolved for a rat's kidneys, unveiling detailed cortical-medullary anatomy and renal physiological functions. The newly developed GSH-IO NPs thus open a new dimension in efforts towards high-performance, long-circulating MRI contrast agents that have biotargeting potential.

Antiferromagnetic iron nanocolloids: a new generation in vivo T1 MRI contrast agent.

A novel T1 agent, antiferromagnetic α-iron oxide-hydroxide (α-FeOOH) nanocolloids with a diameter of 2-3 nm, has been successfully prepared. These nanocolloids, together with a post synthetic strategy performed in mesoporous silica, are a great improvement over the low T1-weighted contrast common in traditional magnetic silica nanocomposites. The intrinsic antiferromagnetic goethite (α-FeOOH) shows very low magnetization (M(z)) of 0.05 emu g(-1) at H = 2 T at 300 K (0.0006 emu g(-1) for FeOOH/WMSN-PEG), which is 2 orders of magnitude smaller than any current ultrasmall iron oxide NPs (>5 emu g(-1)) reported to date, hence ensuring the low r2 (∝ Mz) (7.64 mM(-1) s(-1)) and r2/r1 ratio (2.03) at 4.7 T. These biodegradable α-FeOOH nanocolloids also demonstrate excellent in vitro cellular imaging and in vivo MR vascular and urinary trace imaging capability with outstanding biocompatibility, which is exceptionally well secreted by the kidney and not the liver as with most nanoparticles, opening up a new avenue for designing powerful antiferromagnetic iron T1 contrast agents.

Photothermal cancer therapy via femtosecond-laser-excited FePt nanoparticles.

FePt nanoparticles (NPs) have recently been revealed to be significant multifunctional materials for the applications of biomedical imaging, drug delivery and magnetic hyperthermia due to their novel magnetic properties. In this study, a newly discovered photothermal effect activated by the near infrared (NIR) femtosecond laser for FePt NPs was demonstrated. The threshold laser energy to destroy cancer cells was found to be comparable to that of gold nanorods (Au NRs) previously reported. Through the thermal lens technique, it was concluded that the temperature of the FePt NPs can be heated up to a couple of hundreds degree C in picoseconds under laser irradiation due to the excellent photothermal transduction efficiency of FePt NPs. This finding boosts FePt NPs versatility in multifunctional targeted cancer therapy.

Direct evidence of type II band alignment in nanoscale P3HT/CdSe heterostructures.

Due to inherent advantages of both constituent materials, organic/inorganic hybrid composites have attracted increasing attention. One of the fundamental issues needed to be resolved is their band alignment, which governs most of the electrical and optical properties. Here, we report the investigation of optical transition in poly(3-hexylthiophene) (P3HT)/CdSe nano-composites (NCs). It is found that the relaxation dynamics of photo-carriers in NCs is dominated by charge separation effects. Based on the band bending effect and the quantum confinement energy of electrons in the conduction band of CdSe quantum dots, we provide direct evidence of type II band alignment in P3HT/CdSe NCs. The establishment of a type II transition in NCs is very useful for the future design of efficient optoelectronic devices based on conjugated polymer/semiconductor hybrid systems.

In vitro and in vivo studies of FePt nanoparticles for dual modal CT/MRI molecular imaging.

The water-solvable FePt nanoparticles of 3, 6, and 12 nm in diameter (3 nm-, 6 nm-, and 12 nm-FePt) were synthesized and applied as a dual modality contrast agent for CT/MRI molecular imaging. These nanoparticles present excellent biocompatibility and hemocompatibility in all test concentrations for the imaging contrast. The biodistribution analysis revealed the highest serum concentration and circulation half-life for 12 nm-FePt, followed by 6 nm-FePt then 3 nm-FePt. Thus, the 3 nm-FePt showed higher brain concentrations. Anti-Her2 antibody conjugated FePt nanoparticles demonstrated molecular expression dependent CT/MRI dual imaging contrast effect in MBT2 cell line and its Her2/neu gene knock out counterpart. Selective contrast enhancement of Her2/neu overexpression cancer lesions in both CT and MRI was found in tumor bearing animal after tail vein injection of the nanoparticles. The 12 nm-FePt outperformed 3 nm-FePt in both imaging modalities. These results indicate the potential of FePt nanoparticles to serve as novel multimodal molecular imaging contrast agents in clinical settings.

Effects of glutathione on amyloid fibrillation of hen egg-white lysozyme.

This study examined the effects of glutathione on the fibrillation of hen egg-white lysozyme. We found that the fibrillation of lysozyme was considerably reduced by GSH while no anti-aggregating activity was detected with only GSSG. SDS-PAGE results also revealed that the addition of GSH led to an early occurrence of prominent lysozyme hydrolysis. Moreover, GSH was effective in inhibiting lysozyme fibrillation when GSH was added within 6 days of incubation. We conclude that the attenuation of lysozyme fibrillation is strongly dependent upon the redox environment. Our data may contribute to decipher the molecular mechanism of amyloid fibrillation.

Inhibition of amyloid fibril formation of beta-amyloid peptides via the amphiphilic surfactants.

Beta-amyloid peptide (A beta) is the major proteinacious constituent of senile plaques in Alzheimer's disease and is believed to be responsible for the neurodegeneration process associated with the disease. While the actual size of the aggregated species responsible for A beta neurotoxicity and fibrillogenesis mechanism(s) remain unknown, retardation of A beta aggregation still holds assurance as an effective strategy in reducing A beta-elicited toxicity. The research presented here is aimed at examining the inhibitory effect of two amphiphilic surfactants, di-C6-PC and di-C7-PC, on the in vitro fibrillogenesis process of A beta(1--40) peptides at physiological pH (pH 7.2). Using ThT-induced fluorescence, turbidity, Congo red binding, and circular dichroism spectroscopy studies, our research demonstrated that the inhibition of A beta(1--40) fibril formation was di-C6-PC and di-C7-PC concentration-dependent. The best inhibitory action on fibril formation was observed when A beta was incubated with di-C7-PC at 100 microM over time. We believe that the outcome from this work will aid in the development and/or design of potential inhibitory agents against amyloid formation associated with Alzheimer's and other amyloid diseases.