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We report an intelligent theranostic nanoprobe based on Mn3O4 tetragonal bipyramids, which boost MRI relaxivity and chemodynamic capacity upon simultaneous responding to H+ and GSH, for precise diagnosis and suppression of solid tumor and metastasis.

Photosensitizer in photodynamic therapy (PDT) accumulates in both tumor and adjacent normal tissue due to low selective biodistribution, results in undesirable side effect with limited clinic application. Herein, an intelligent nanoplatform is reported that selectively acts as reactive oxygen species (ROS) scavenger in normal tissue but as ROS generator in tumor microenvironment (TME) to differentially control ROS level in tumor and surrounding normal tissue during PDT. By down-regulating the produced ROS with dampened cytokine wave in normal tissue after PDT, the nanoplatform reduces the inflammatory response of normal tissue in PDT, minimizing the side effect and tumor metastasis in PDT. Alternatively, the nanoplatform switches from ROS scavenger to generator through the glutathione (GSH) responsive degradation in TME, which effectively improves the PDT efficacy with reduced GSH level and amplified oxidative stress in tumor. Simultaneously, the released Mn ions provide real-time and in situ signal change of magnetic resonance imaging (MRI) to monitor the reversal process of catalysis activity and achieve accurate tumor diagnosis. This TME-responsive ROS scavenger/generator with activable MRI contrast may provide a new dimension for design of next-generation PDT agents with precise diagnosis, high therapeutic efficacy, and low side effect.

Engineered magnetic nanoparticles have been extensively explored for magnetic resonance imaging (MRI) diagnosis of a tumor to improve the visibility. However, most of these nanoparticles display "always-on" signals without tumor specificity, causing insufficient contrast and false positives. Here, we provide a new paradigm of MRI diagnosis using MnCO3 nanorhombohedras (MnNRs) as an ultrasensitive T1-weighted MRI contrast agent, which smartly enhances the MR signal in response to the tumor microenvironment. MnNRs would quickly decompose and release Mn2+ at mild acidity, one of the pathophysiological parameters associated with cancer malignancy, and then Mn2+ binds to surrounding proteins to achieve a remarkable amplification of T1 relaxivity. In vivo MRI experiments demonstrate that MnNRs can selectively brighten subcutaneous tumors from the edge to the interior may be because of the upregulated vascular permeation at the tumor edge, where cancer cell proliferation and angiogenesis are more active. Specially, benefiting from the T2 shortening effect in normal liver tissues, MnNRs can detect millimeter-sized liver metastases with an ultrahigh contrast of 294%. The results also indicate an effective hepatic excretion of MnNRs through the gallbladder. As such, this pH-activatable MRI strategy with facility, biocompatibility, and excellent efficiency may open new avenues for tumor malignancy and metastasis diagnosis and holds great promise for precision medicine.

Engineered magnetic nanoparticles have been extensively explored for magnetic resonance imaging (MRI) diagnosis of a tumor to improve the visibility. However, most of these nanoparticles display "always-on" signals without tumor specificity, causing insufficient contrast and false positives. Here, we provide a new paradigm of MRI diagnosis using MnCO

Thin copper substrates in precision physical experiments are commonly machined by double-sided lapping to obtain high flatness. However, the flatness is limited by the accuracy of lapping plate, process vibration and so on in double-sided lapping process. Hence, magnetorheological finishing (MRF) with its good performance on profile modification is employed to improve the flatness. Nevertheless, thin copper substrates, which are sensitive to the stress, deformed easily with uneven material removal on the surface. In this paper, MRF is conducted on machining thin copper substrate for the first time considering deformation induced by stress. A finite element model is established to evaluate the deformation by residual stress, and the results show that the deformation tends to be more serious with the increase of the material removal. According to the simulation results, the material removal is optimized considering both deformation and efficiency, and a series of experiments are conducted on a Φ100×2.8 mm workpiece to verify the simulation results. The experimental results show that the flatness is further improved from peak to valley (PV) 6.6 μm to PV 2.3 μm with optimized processing parameters. Hence, the feasibility of magnetorheological finishing on thin copper substrate is demonstrated.

In this work, we have demonstrated that mesoporous silica-coated Pd@Ag nanoparticles (Pd@Ag@mSiO

(19)F magnetic resonance imaging ((19)F MRI) is a promising technique for in vivo molecular imaging and clinical diagnosis, benefiting from its negligible background and unlimited tissue penetration depth. However, the development of (19)F probes with good water solubility and versatile functions for bioresponsive and practical applications remains a challenge. Here, we report fluorinated ion liquids (ILs) as a new type of fluorine agents and build a fluorinated ionic liquid-based activatable (19)F MRI platform (FILAMP), which relies on the phase transition of ILs. Upon exposure to environmental stimulation, coating polymer dissolves or degrades to release the fluorinated ILs payload, which rapidly enhances (19)F signal. This “turn-on” response is verified by the successful detection of biological targets (for example, dysregulated pH and MMP overexpression) at the cellular level and in mice, demonstrating the potential of FILAMP as a robust activatable (19)F probe for diagnosis and monitoring of biological and pathological processes.

Sensitive detection of matrix metalloproteinase 2 (MMP-2, an important cancer marker associated with tumor invasion and metastasis) activity in vitro and at cellular level is of great significance to clinical diagnosis and medical treatment. With unique physical properties, nanoparticles are emerging as a platform for the construction of conjugates of various biological molecules, which can be expected to generate new types of biosensors. In this work, Fe3O4 NPs were modified with Gd chelates via linking peptides to construct NP–substrate (Fe3O4–pep–Gd) conjugates for kinetic MMP-2 activity assessment in vitro at the cellular level and in vivo. Superparamagnetic Fe3O4 quenched the longitudinal relaxation effect (T1 relaxivity) of the attached Gd chelates by perturbing proton relaxation process under an external magnetic field. MMP-2 cleaved the peptide substrates and released Gd chelates from the local magnetic fields accompanied by T1 relaxivity recovery and T1 contrast enhancement. Benefiting from signa...

Iron materials are widely applied in electrical-tower. However, the freezing rain adhering to the electric-tower in winter can raise a huge potential safety hazard to the power facilities. Therefore, how to make ironworks possess anti-icing property has become a difficult problem. In order to resolve the aforementioned issue, a facile, low-cost and environment-friendly electrochemical machining method was developed to fabricate superhydrophobic surface on iron materials to endow anti-icing capacity in the freezing rain. After fluoroalkylsilane (FAS) modification, superhydrophobic surface could be obtained. The morphology of the surface film was examined using scanning electron microscopy (SEM) equipped with an energy-dispersive spectroscopy (EDS) and laser confocal microscope. The chemical composition was investigated by X-ray photoelectron spectroscopy (XPS). The influence of the applied processing time on wettability was also studied. The results showed that a rough surface, which consisted of many step-like structures, was formed on the surface of iron by the proposed electrochemical method. After FAS modification, the surface showed good superhydrophobicity with the water contact angle of 162° and water sliding angle of 3.33°. The mechanism of the generated rough structures was also discussed. Moreover, the static and dynamic anti-icing tests were conducted. The results showed that the superhydrophobic surface can not only significantly delay the freezing time, but also prevent the cold water from freezing on the iron surface, which could be a good solution to the freezing rain issue.

Cation exchange is a powerful means to adjust the properties of nanocrystals through composition change with morphology retention. Herein, we demonstrate that cation exchange can engineer the composition of iron oxide nanocrystals to dramatically improve their contrast ability in magnetic resonance imaging (MRI). We successfully construct manganese and zinc engineered iron oxide nanoparticles with diverse shapes (sphere, cube, and octapod) by facile cation exchange reactions. Extended X-ray absorption fine structure (EXAFS) study indicates that Mn2+ and Zn2+ ions are doped into the crystal lattice of ferrite, and more importantly, most of them are distributed in Td sites of ferrite. These engineered shaped-anisotropic iron oxide nanoparticles exhibit both high saturated magnetization and large effective boundary radii, which leads to remarkable transverse relaxivity (r2), for example, 754.2 mM–1 s–1 for zinc engineered octapod iron oxide nanoparticles. These engineered iron oxide nanoparticles, as high-pe...

Arsenic trioxide has achieved great clinical success in the treatment of acute promyelocytic leukemia (APL). However, it is difficult to replicate the success in other cancers, such as solid tumors, in part because of the rapid renal clearance and dose-limiting toxicity. Nanotechnology is expected to overcome these disadvantages through altering its pharmacokinetics and concentrating the drug at the desired sites. Herein, we report a "one-pot" method to develop arsenic-based nanodrugs by in situ coating the as-prepared arsenic nanocomplexes with porous silica shells. This process can be easily reproduced and scaled up because no complicated synthesis and purification steps are involved. This core-shell embedding method endows nanodrugs with high loading capacity (57.9 wt%) and a prolonged pH-responsive releasing profile, which is crucial to increase the drug concentration at tumor sites and improve the drug efficacy. Based on these unique features, the nanodrugs significantly inhibit the growth of solid tumors without adverse side effects. Therefore, we anticipate that the arsenic-based nanodrugs generated by this facile synthetic route may be a powerful and alternative strategy for solid tumor therapy.

Controlled synthesis of monodisperse iron oxide (IO) nanostructures with diverse morphology remains a major challenge. In this work, IO nanostructures with various shapes and surface structures were synthesized by thermal decomposition of iron oleate (FeOL) in the presence of sodium oleate (NaOL). In a mild condition using 1-octadecene (ODE) as solvent, NaOL may preferentially bind to Fe3O4{111} facets and lead to the formation of Fe3O4{111} facet exposed IO plates, truncated octahedrons, and tetrahedrons. While in a high-boiling temperature tri-n-octylamine (TOA) solvent, we obtained Fe3O4{100} facet exposed IO cubes, concaves, multibranches, and assembled structures by varying the molar ratios of NaOL/FeOL. Moreover, we demonstrated that IO nanoparticles (NPs) with metal-exposed surface structures have enhanced T1 relaxation time shortening effects to protons, and IO NPs with anisotropic shapes are superior in protons T2 relaxation shortening due to the larger effective radii compared to that of spheric...

Delivery of arsenic trioxide (ATO), a clinical anticancer drug, has drawn much attention to improve its pharmacokinetics and bioavailability for efficient cancer therapy. Real-time and in situ monitoring of ATO behaviors in vivo is highly desirable for efficient tumor treatment. Herein, we report an ATO-based multifunctional drug delivery system that efficiently delivers ATO to treat tumors and allows real-time monitoring of ATO release by activatable T1 imaging. We loaded water-insoluble manganese arsenite complexes, the ATO prodrug, into hollow silica nanoparticles to form a pH-sensitive multifunctional drug delivery system. Acidic stimuli triggered the simultaneous release of manganese ions and ATO, which dramatically increased the T1 signal (bright signal) and enabled real-time visualization and monitoring of ATO release and delivery. Moreover, this smart multifunctional drug delivery system significantly improved ATO efficacy and strongly inhibited the growth of solid tumors without adverse side effects. This strategy has great potential for real-time monitoring of theranostic drug delivery in cancer diagnosis and therapy.

Sensitive detection of matrix metalloproteinase 2 (MMP-2, an important cancer marker associated with tumor invasion and metastasis) activity in vitro and at cellular level is of great significance to clinical diagnosis and medical treatment. With unique physical properties, nanoparticles are emerging as a platform for the construction of conjugates of various biological molecules, which can be expected to generate new types of biosensors. In this work, Fe

In a recent publication (Wang et al., Appl. Phys. Lett. 100 (2012) 051108), we reported experimental generation of a partially coherent radially polarized (RP) beam. In this paper, based on the unified theory of coherence and polarization, we derive the analytical expressions for the elements of the cross-spectral density matrix of a partially coherent RP beam propagating through an astigmatic optical system. As an application example, we study numerically the effect of astigmatism of the optical system on the focusing properties of a partially coherent RP beam. Our results show that the astigmatism of the optical system can be used for modulating the statistical properties of a focused partially coherent RP beam, which will be useful for beam shaping and particle trapping.

Multifunctional nanostructures combining diagnosis and therapy modalities into one entity have drawn much attention in the biomedical applications. Herein, we report a simple and cost-effective method to synthesize a novel cubic Au nano-aggregates structure with edge-length of 80 nm (Au-80 CNAs), which display strong near-infrared (NIR) absorption, excellent water-solubility, good photothermal stability, and high biocompatibility. Under 808 nm laser irradiation for 5 min, the temperature of the solution containing Au-80 CNAs (100 μg/mL) increased by ~38 °C. The in vitro and in vivo studies demonstrated that Au-80 CNAs could act as both photothermal therapeutic (PTT) agents and photoacoustic imaging (PAI) contrast agents, indicating that the only one nano-entity of Au-80 CNAs shows great potentials for theranostic applications. Moreover, this facile and cost-effective synthetic method provides a new strategy to prepare stable Au nanomaterials with excellent optical properties for biomedical applications.

In the work, a novel multifunctional silica-based nanoplatform (Pd@Ag@SiO2(RITC)-R8) for bioimaging and photothermal therapy (PTT) of cancer cells has been developed. The Pd@Ag nanosheets encapsulated inside silica can act as effective near-infrared (NIR) absorbers for cancer photothermal therapy. Fluorescent dye, rhodamine B isothiocyanate (RITC), was covalently doped into the silica network to provide the capacity for optical imaging. After amine modification, the Pd@Ag@SiO2(RITC)-NH2 can be further conjugated with octaarginine (R8, a cell penetrating peptide) for enhancing the uptake of nanoparticles by cells. Confocal fluorescent images and flow cytometry analysis revealed that R8-conjugated nanoparticles (Pd@Ag@SiO2(RITC)-R8) were taken up by cells more efficiently. Correspondingly, the optical imaging and photothermal therapeutic efficiency of Pd@Ag@SiO2(RITC)-R8 upon cancer cells were also raised due to their higher cellular uptake when compared with that of Pd@Ag@SiO2(RITC)-NH2. Our results indicate that these multifunctional Pd@Ag@SiO2(RITC)-R8 may have great potential for applications in imaging-guided cancer photothermal therapy.

The innovative applications of engineered nanoparticles (NPs) in medicine, such as diagnosis and therapy, have attracted considerable attention. It is highly important to predict the interactions between engineered NPs and the complex biological system as well as the impacts on the subsequent behaviors in living subjects. Herein, we report the use of T1 contrast-enhanced magnetic resonance imaging (MRI) to monitor the in vivo behaviors of NPs in a real-time manner. We chose ultrasmall Pd nanosheets (SPNSs) as the object of NPs because of their promise in theranostics and fitness for diverse surface chemistry. SPNSs were modified with different surface coating ligands (e.g., polyethylene glycol, zwitterionic ligands, polyethylenimine) and functionalized with Gd-chelates to render T1 contrast-enhanced capability. MRI real-time monitoring recorded the location and accumulation of SPNSs in small animals and revealed the prominent roles of surface coating ligands in pharmacokinetics. These results highlighted the significance of selecting proper surface coating for particular biomedical assignment. Moreover, we demonstrated a powerful and noninvasive means to predict and detect the behaviors of NPs in living subjects, which may be helpful for rational design and screening of engineered NPs in biomedical applications.

We report a simple strategy to construct a multiple gadolinium complex decorated fullerene (CGDn) as an enhanced T1 contrast agent. The CGDn exhibits much higher T1 relaxivity (∼49.7 mM(-1) s(-1)) than individual Gd-DOTA, and shows excellent T1 contrast enhancement ability both in vitro and in vivo.

Magnetic resonance angiography using gadolinium-based molecular contrast agents suffers from short diagnostic window, relatively low resolution and risk of toxicity. Taking into account the chemical exchange between metal centers and surrounding protons, magnetic nanoparticles with suitable surface and interfacial features may serve as alternative T1 contrast agents. Herein, we report the engineering on surface structure of iron oxide nanoplates to boost T1 contrast ability through synergistic effects between exposed metal-rich Fe3O4(100) facets and embedded Gd2O3 clusters. The nanoplates show prominent T1 contrast in a wide range of magnetic fields with an ultrahigh r1 value up to 61.5 mM(-1) s(-1). Moreover, engineering on nanobio interface through zwitterionic molecules adjusts the in vivo behaviors of nanoplates for highly efficient magnetic resonance angiography with steady-state acquisition window, superhigh resolution in vascular details, and low toxicity. This study provides a powerful tool for sophisticated design of MRI contrast agents for diverse use in bioimaging applications.

Multifunctional nanostructures with both diagnostic and therapeutic capabilities have attracted considerable attention in biomedical research because they can offer great advantages in disease management and prognosis. In this work, a facile way to transfer the hydrophobic iron oxide (IO) nanoparticles into aqueous media by employing carboxylic graphene oxide (GO-COOH) as the transferring agent has been reported. In this one-step process, IO nanoparticles adhere to GO-COOH and form water-dispersible clusters via hydrophobic interactions between the hydrophobic ligands of IO nanoparticles and the basal plane of GO-COOH. The multiple IO nanoparticles on GO-COOH sheets (IO/GO-COOH) present a significant increase in T2 contrast enhancement. Moreover, the IO/GO-COOH nanoclusters also display a high photothermal conversion efficiency and can effectively inhibit tumor growth through the photothermal effects. It is envisioned that such IO/GO-COOH nanocomposites combining efficient MRI and photothermal therapy hold great promise in theranostic applications.

Tyrosinase is an important marker of human diseases such as the neurodegeneration associated with Parkinson's disease and melanoma. Sensitive detection of tyrosinase activity in vitro and inside cells is of great significance to medical diagnostics and skin disorder treatments. With unique photophysical properties, semiconductor quantum dots (QDs) are employed as photoluminescent platforms for various biosensing, in particular for the detection of enzyme activities. In this work, QDs are functionalized with tyrosine and zwitterionic molecules to construct a nanometer-scale scaffold (QD-Tyr conjugate), and this is used to test tyrosinase activity in vitro and inside cells. Tyrosinase oxidizes tyrosine to dopachrome and switches on the electron-transfer access, which relates to fluorescence quenching. High quenching efficiency is achieved by shortening the distance between the electron donors and acceptors, which is attributed to the small size of the conjugated tyrosine. Enzymatic process curves reveal the enhanced enzymatic activity on the conjugated nanoparticle substrate, which leads to highly sensitive detection of tyrosinase (as low as 1 nM). It is also demonstrated that QD-Tyr conjugates can sensitively probe intracellular tyrosinase in melanoma cells, which promises great potential in disease monitoring and medical diagnostics.