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We describe here a method to generate both benzoyl fluorides and benzoic acids using 2,5-cyclohexadienones prepared from phenols.

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.

Iron oxide nanoparticle (IONP) with unique magnetic property and high biocompatibility have been widely used as magnetic resonance imaging (MRI) contrast agent (CA) for long time. However, a review which comprehensively summarizes the recent development of IONP as traditional T2 CA and its new application for different modality of MRI, such as T1 imaging, simultaneous T2/T1 or MRI/other imaging modality, and as environment responsive CA is rare. This review starts with an investigation of direction on the development of high-performance MRI CA in both T2 and T1 modal based on quantum mechanical outer sphere and Solomon–Bloembergen–Morgan (SBM) theory. Recent rational attempts to increase the MRI contrast of IONP by adjusting the key parameters, including magnetization, size, effective radius, inhomogeneity of surrounding generated magnetic field, crystal phase, coordination number of water, electronic relaxation time, and surface modification are summarized. Besides the strategies to improve r2 or r1 values, strategies to increase the in vivo contrast efficiency of IONP have been reviewed from three different aspects, those are introducing second imaging modality to increase the imaging accuracy, endowing IONP with environment response capacity to elevate the signal difference between lesion and normal tissue, and optimizing the interface structure to improve the accumulation amount of IONP in lesion. This detailed review provides a deep understanding of recent researches on the development of high-performance IONP based MRI CAs. It is hoped to trigger deep thinking for design of next generation MRI CAs for early and accurate diagnosis.

Cytochrome P450 1B1 (CYP1B1) is highly expressed in a variety of tumors and implicated to drug resistance. More and more researches have suggested that CYP1B1 is a new target for cancer prevention and therapy. Various CYP1B1 inhibitors with a rigid polycyclic skeleton have been developed, such as flavonoids, trans-stilbenes, and quinazolines. To obtain a new class of CYP1B1 inhibitors, we designed and synthesized a series of bentranil analogues, moreover, IC

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.

Introduction and objective Precisely and sensitively diagnosing diseases especially early and accurate tumor diagnosis in clinical magnetic resonance (MR) scanner is a highly demanding but challenging task. Gadolinium (Gd) chelate is the most common T 1 magnetic resonance imaging (MRI) contrast agent at present. However, traditional Gd-chelates are suffering from low relaxivity, which hampers its application in clinical diagnosis. Currently, the development of nano-sized Gd based T 1 contrast agent, such as incorporating gadolinium chelate into nanocarriers, is an attractive and feasible strategy to enhance the T 1 contrast capacity of Gd chelate. The objective of this study is to improve the T 1 contrast ability of Gd-chelate by synthesizing nanoparticles (NPs) for accurate and early diagnosis in clinical diseases. Methods Reverse microemulsion method was used to coat iron oxide (IO) with tunable silica shell and form cores of NPs IO@SiO2 at step one, then Gd-chelate was loaded on the surface of silica-coated iron oxide NPs. Finally, Gd-based silica coating magnetite NPs IO@SiO2-DTPA-Gd was developed and tested the ability to detect tumor cells on the cellular and in vivo level. Results The r 1 value of IO@SiO2-DTPA-Gd NPs with the silica shell thickness of 12 nm was about 33.6 mM-1s-1, which was approximately 6 times higher than Gd-DTPA, and based on its high T 1 contrast ability, IO@SiO2-DTPA-Gd NPs could effectively detect tumor cells on the cellular and in vivo level. Conclusion Our findings revealed the improvement of T 1 relaxation was not only because of the increase of molecular tumbling time caused by the IO@SiO2 nanocarrier but also the generated magnetic field caused by the IO core. This nanostructure with high T 1 contrast ability may open a new approach to construct high-performance T 1 contrast agent.

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

The nascent field of theranostics, which couples targeted therapy with diagnostics, has catalyzed efforts toward improved nanoprobe designs that facilitate both localized treatment and diagnostic imaging. Rare-earth-doped nanoparticles (RENPs) have emerged as a leading candidate for theranostics because of their versatile synthesis and modification chemistries, photostability, and relative safety. Furthermore, their bright, tunable fluorescence using near-infrared (NIR) excitation enables multispectral imaging with high signal-to-background ratios. In this work, we have synthesized double-shelled RENPs with tunable properties for optimal fluorescent imaging, photoacoustic imaging, and photothermal therapy. The properties of the double-shelled RENPs were tailored by controlling the density of rare-earth ions (i.e., activator or sensitizer) by using either a functional amorphous organic or a crystalline outermost shell. This study systematically analyzes the effects of the functional organic or inorganic outermost shell on the imaging and photothermal conversion properties of our RENPs. Despite the weaker infrared absorption enhancement, the functional organic outermost shell impregnated with a low density of rare-earth ions led to minimal reduction of fluorescence emissions. In contrast, the higher density of rare-earth ions in the inorganic shell led to higher infrared absorption and consequently significant reduction in emissions arising from the undesired optical attenuation. Inorganic shell thickness was therefore modified to reduce the deleterious attenuation, leading to brighter emissions that also enabled the in vitro SWIR detection of ∼2500 cells/cluster. Using the enhanced infrared properties that arise from this functional inorganic layer, which could be engineered to respond to either NIR or SWIR, we demonstrated that (1) bright SWIR emissions allowed detection of small cell clusters; (2) strong PA signals allowed clear visualization of particle distribution within tumors; and (3) strong photothermal effects resulted in localized elevated temperatures. Collectively, these results highlight the utility of these double-shelled RENPs as theranostic agents that are compatible with both photoacoustic or fluorescent imaging platforms.

Arsenic trioxide is a clinical drug that can be used to successfully treat acute promyelocytic leukemia. However, its therapeutic effect on solid tumors is limited because of the poor pharmacokinetics and dose-limiting toxicity. Here, we report a facile strategy to achieve high anticancer activity of arsenic trioxide by loading the nanoparticulate prodrug into hollow silica inorganic nanoparticles. Because of the appropriate size, pH sensitivity, and surface targeted modification, this smart nanosized drug system can deliver arsenic trioxide into cancer cells efficiently and exhibits much higher cytotoxicity to a variety of cancer cells than free arsenic trioxide. Moreover, this nanomedicine can further promote the differentiation and inhibit the migration of cancer cells. In vivo results suggest that this drug delivery system can significantly inhibit the growth of solid tumors without adverse side effects. This study highlights a feasible drug delivery strategy to expand the use of arsenic trioxide for the effective treatment of solid tumors.

Magnetite nanoparticles, with good biocompatibility and favorable magnetic properties, have the potential to be the best candidate for non-gadolinium MRI contrast agents. However, they usually show low T

Mn(iv)-Based nanoparticles (NPs) are effective in improving tumor oxygenation (hypoxia) and reducing endogenous hydrogen peroxide and acidity in the tumor region. However, the optimized reduction conditions of conventional Mn(iv)-based NPs are generally reported at pH ≤ 6.5, while the usual pH range of the tumor microenvironment (TME) is 6.5-7.0. The dissatisfactory imaging performance in the weakly acidic environment may limit their further application in tumor diagnosis. In this study, Mn(iii) was introduced in a nanoplatform, because it is reduced into Mn(ii) in weakly acidic environments. Arg-Gly-Asp (RGD) peptide-decorated bovine serum albumin (BSA) was employed as the stabilizer and scaffold to fabricate Mn(iii)- and Mn(iv)-integrated nanocomposites (RGD-BMnNPs) with suitable size, good stability, and excellent biocompatibility. The as-prepared NPs showed clear contrast enhancement at pH 6.5-6.9 in vitro as well as sensitive and rapid T1-weighted imaging performance within the tumor region in a glioblastoma (U87MG) orthotopic model, owing to the intrinsic disproportionation reaction of Mn(iii) in the weakly acidic environment. In addition, these NPs could be used for efficient siRNA delivery. They showed superior advantages in this process, including increased tumour uptake, improved tumor accumulation and enhanced therapeutic effects with the modulation of the TME. These novel albumin-stabilized manganese-based NPs combined with efficient drug delivery capacity hold great potential to serve as intelligent theranostic agents for further clinical translation.

Developing stable and efficient bifunctional catalysts for overall water splitting is a critical step in the production of renewable energy sources. Here we report a stable and highly active electrocatalyst comprised of NiCoSe2-x/N-doped carbon mushroom-like core/shell nanorods on silk-derived carbon fiber through one step selenization. The unique one-dimensional nanorod structure facilitates the charge transport, and the N-doped carbon shell also increases the electrical conductivity, resulting in a remarkable enhancement of the catalytic activity. The N-doped carbon shell also functions as a protection layer. The composite catalyst therefore exhibits outstanding OER and HER performance, it can also stably drive the overall water splitting at a low cell voltage of 1.53 V in base solution. The present work provides an efficient strategy for the fabrication of stable and active electrocatalysts with earth-abundant elements.

Gene therapy is emerging as the next generation of therapeutic modality with United States Food and Drug Administration approved gene-engineered therapy for cancer and a rare eye-related disorder, but the challenge of real-time monitoring of on-target therapy response remains. In this study, we have designed a theranostic nanoparticle composed of shortwave-infrared-emitting rare-earth-doped nanoparticles (RENPs) capable of delivering genetic cargo and of real-time response monitoring. We showed that the cationic coating of RENPs with branched polyethylenimine (PEI) does not have a significant impact on cellular toxicity, which can be further reduced by selectively modifying the surface characteristics of the PEI coating using counter-ions and expanding their potential applications in photothermal therapy. We showed the tolerability and clearance of a bolus dose of RENPs@PEI in mice up to 7 days after particle injection in addition to the RENPs@PEI ability to distinctively discern lung tumor lesions in a breast cancer mouse model with an excellent signal-to-noise ratio. We also showed the availability of amine functional groups in the collapsed PEI chain conformation on RENPs, which facilitates the loading of genetic cargo that hybridizes with target gene in an in vitro cancer model. The real-time monitoring and delivery of gene therapy at on-target sites will enable the success of an increased number of gene- and cell-therapy products in clinical trials.

Magnetite nanoparticles, with good biocompatibility and favorable magnetic properties, have the potential to be the best candidate for non-gadolinium MRI contrast agents. However, they usually show low T1 contrast ability, largely because Fe(II) ions have a short electronic relaxation time and also have a small number of unpaired electrons with inefficient proton relaxation enhancement. Herein, we report a novel strategy to increase the T1 contrast ability of magnetite nanoparticles, through substituting the undesirable Fe(II) ions with Mn(II) ions. Mn(II) ions have a longer electronic relaxation time (10−8 s) and more unpaired electrons (5 unpaired electrons). We successfully construct diverse-shaped manganese ferrite nanoparticles with abundant magnetic ions, Mn(II) and Fe(III), exposed on the surface. These manganese ferrite nanoparticles exhibit remarkably higher longitudinal relaxivity than their parent iron oxide nanoparticles. We demonstrate that the increase in T1 relaxivity is attributed to the extended electronic relaxation time and the increased number of unpaired electrons on the surface of the nanoparticles by controlling surface features, particularly by adjusting the substitution degree of Mn(II) ions and in situ coating. This study provides an insightful strategy to improve the T1 contrast ability of iron oxide nanoparticles, which is urgently needed for developing high-performance non-gadolinium T1 contrast agents for imaging and diagnosis of disease.

Since manganese oxide nanomaterials attract wide attention in the biomedical and energy fields, understanding the inner relationship between their properties and structures is fundamental and urgently needed. However, controllable synthesis of metal oxide nanomaterials with diverse morphologies is still a persistent challenge. Herein, various anisotropic manganese oxide nanostructures from zero-dimensional (0-D) to three-dimensional (3-D) were successfully fabricated through thermal decomposition. We observed that chloride ions can assist the formation of 0-D nanooctaherals, nanocubes, and nanooctapods due to its binding capacity to the manganese ions on the nanocrystal surface. Interestingly, the procedural heating process can affect the decomposition rate of the manganese–oleate, which drives a substantial reduction in the surface free energy by sharing a common crystallographic orientation and leads to the formation of 1-D and 3-D nanostructures by oriented attachment growth. On the basis of systematic...

Engineering interfacial structure of biomaterials have drawn much attention due to it can improve the diagnostic accuracy and therapy efficacy of nanomedicine, even introducing new moiety to construct theranostic agents. Nanosized magnetic resonance imaging contrast agent holds great promise for the clinical diagnosis of disease, especially tumor and brain disease. Thus, engineering its interfacial structure can form new theranostic platform to achieve effective disease diagnosis and therapy. In this study, we engineered the interfacial structure of typical MRI contrast agent, Gd2O3, to form a new theranostic agent with improved relaxivity for MRI guided synergetic chemodynamic/photothermal therapy. The synthesized Mn doped gadolinium oxide nanoplate exhibit improved T1 contrast ability due to large amount of efficient paramagnetic metal ions and synergistic enhancement caused by the exposed Mn and Gd cluster. Besides, the introduced Mn element endow this nanomedicine with the Fenton-like ability to generate OH from excess H2O2 in tumor site to achieve chemodynamic therapy (CDT). Furthermore, polydopamine engineered surface allow this nanomedicine with effective photothermal conversion ability to rise local temperature and accelerate the intratumoral Fenton process to achieve synergetic CDT/photothermal therapy (PTT). This work provides new guidance for designing magnetic resonance imaging guided synergetic CDT/PTT to achieve tumor detection and therapy.

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.

High-performance magnetic resonance imaging (MRI) contrast agents and novel contrast enhancement strategies are urgently needed for sensitive and accurate diagnosis. Here we report a strategy to construct a new T1 contrast agent based on the Solomon-Bloembergen-Morgan (SBM) theory. We loaded the ultrasmall gadolinium oxide nanoparticles into worm-like interior channels of mesoporous silica nanospheres (Gd2O3@MSN nanocomposites). This unique structure endows the nanocomposites with geometrical confinement, high molecular tumbling time, and a large coordinated number of water molecules, which results in a significant enhancement of the T1 contrast with longitudinal proton relaxivity (r1) as high as 45.08 mM(-1) s(-1). Such a high r1 value of Gd2O3@MSN, compared to those of ultrasmall Gd2O3 nanoparticles and gadolinium-based clinical contrast agents, is mainly attributed to the strong geometrical confinement effect. This strategy provides new guidance for developing various high-performance T1 contrast agents for sensitive imaging and disease diagnosis.

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.

Iron oxide has been developed as either T1 or T2 magnetic resonance imaging (MRI) contrast agents by controlling the size and composition; however, the underlying mechanism of T1 and T2 contrasts in one iron oxide entity is still not well understood. Herein, we report that freestanding superparamagnetic magnetite nanoplates with (111) exposed facets have significant but interactional T1 and T2 contrast effects. We demonstrate that the main contribution of the T1 contrast of magnetic nanoplates is the chemical exchange on the iron-rich Fe3O4(111) surfaces, whereas the T2 relaxation is dominated by the intrinsic superparamagnetism of the nanoplates with an enhanced perturbation effect. We are able to regulate the balance of T1 and T2 contrasts by controlling structure and surface features, including morphology, exposed facets, and surface coating. This study provides an insightful understanding on the T1 and T2 contrast mechanisms, which is urgently needed to allow more sophisticated design of high-performance MRI contrast agents.

In this paper, we demonstrate the tunable T1 and T2 contrast abilities of engineered iron oxide nanoparticles with high performance for liver contrast-enhanced magnetic resonance imaging (MRI) in mice. To enhance the diagnostic accuracy of MRI, large numbers of contrast agents with T1 or T2 contrast ability have been widely explored. The comprehensive investigation of high-performance MRI contrast agents with controllable T1 and T2 contrast abilities is of high importance in the field of molecular imaging. In this study, we synthesized uniform manganese-doped iron oxide (MnIO) nanoparticles with controllable size from 5 to 12 nm and comprehensively investigated their MRI contrast abilities. We revealed that the MRI contrast effects of MnIO nanoparticles are highly size-dependent. By controlling the size of MnIO nanoparticles, we can achieve T1-dominated, T2-dominated, and T1-T2 dual-mode MRI contrast agents with much higher contrast enhancement than the corresponding conventional iron oxide nanoparticles.

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.

Hepatocellular carcinoma (HCC) is one of the highest incidences in cancers; however, traditional chemotherapy often suffers from low efficiency caused by drug resistance. Herein, we report an arsenite-loaded dual-drug (doxorubicin and arsenic trioxide, i.e., DOX and ATO) nanomedicine system (FeAsOx@SiO2-DOX, Combo NP) with significant drug synergy and pH-triggered drug release for effective treatment of DOX resistant HCC cells (HuH-7/ADM). This nano-formulation Combo NP exhibits the synergistic effect of DNA damage by DOX along with DNA repair interference by ATO, which results in unprecedented killing efficiency on DOX resistant cancer cells. More importantly, we explored the possible mechanism is that the activity of PARP-1 is inhibited by ATO during the treatment of Combo NP, which finally induces apoptosis of HuH-7/ADM cells by poly (ADP-ribosyl) ation suppression and DNA lesions accumulation. This study provides a smart drug delivery strategy to develop a novel synergistic combination therapy for effectively overcome drug- resistant cancer cells.

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.

Postoperative recurrence and metastasis are the major problems for the current treatment of hepatocellular carcinomas (HCC) in the clinic, including hepatectomy and liver transplantation. Here, we report that arsentic-loaded nanoparticles (ALNPs) are able to reduce the invasion of HCC cells in vitro, and, more importantly, can strongly suppress the invasion and metastasis of HCC in vivo without adverse side effects. Compared to free drug arsenic trioxide , ALNPs can deliver the drug into cancer cells more efficiently, destroy the structure of microtubules and reduce the aggregation of microfilaments in cell membranes more significantly. Furthermore, our results also reveal that tumor cells in murine blood were reduced remarkably after intravenous injection of ALNPs, indicating that this nano-drug may efficiently kill circulating tumor cells in vivo. In conclusion, our nano-drug ALNPs have great potential for the suppression of metastasis of HCC, which may open up a new avenue for the effective treatment of HCC without metastasis and recurrence.

Investigating the surface structure, including crystal surface and surface-coating ligands, of nanoparticulate T1 contrast agent may help to understand the T1 relaxation enhancement in vitro and in vivo. This study presents a novel strategy to develop high-performance T1 magnetic resonance imaging (MRI) contrast agents through optimizing the nanocrystal surface and the nanobio interface. Based on the optimized crystal surface, the novel manganese oxide nanocubes (MOCs) show significantly higher surface-to-volume ratio and an approximately threefold higher r1 value compared to traditional manganese oxide nanospheres. Concurrently, transferring MOCs into aqueous media by dopamine derivatization can avoid the oxidation of Mn(II) ions and provide abundant magnetic core. This optimized surface endows MOCs with a high chemical exchange efficiency during T1 relaxation. Of particular significance, a rationally designed pH-induced charge-switchable surfaces can be negatively charged and corona-free in blood and positively charged surface in tumor sites. This unique feature improves the circulation behavior of this intelligent T1 contrast agent in blood and increases cancer cell uptake to achieve accurate detection of solid tumor, holding great potential in aiding early and precise tumor diagnosis. This study provides a novel tool for sophisticated design of high-performance T1 MRI contrast agents in bioimaging 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.

Recently, some types of MnO nanoparticle (Mn-NP) with favorable imaging capacity have been developed to improve the biocompatible profile of the existing Mn-based MRI contrast agent Mn-DPDP; however, the overall bio-effects and potential toxicity remain largely unknown. In this study, (1)H NMR-based metabolic profiling, integrated with traditional biochemical analysis and histopathological examinations, was used to investigate the absorption, distribution, metabolism, excretion and toxicity of Mn-NPs as candidates for MRI contrast agent. The metabolic responses in biofluids (plasma and urine) and tissues (liver, spleen, kidney, lung and brain) from rats could be divided into four classes following Mn-NP administration: Mn biodistribution-dependent, time-dependent, dose-dependent and complicated metabolic variations. The variations of these metabolites involved in lipid, energy, amino acid and other nutrient metabolism, which disclosed the metabolic fate and biological effects of Mn-NPs in rats. The changes of metabolic profile implied that the disturbance and impairment of biological functions induced by Mn-NP exposure were correlated with the particle size and the surface chemistry of nanoparticles. Integration of metabonomic technology with traditional methods provides a promising tool to understand the toxicological behavior of biomedical nanomaterials and will result in informed decision-making during drug development.

Disclosed are nanoparticles comprising octapod iron oxide having eight trigonal bipyramidal arms and a method of preparing the same. The nanoparticles are prepared by heating a mixture of a ferric carboxylate, a carboxylic acid, a chloride salt, water, and a non-polar solvent, to a temperature above about 300° C. Also disclosed is a method of magnetic resonance imaging a tissue in a mammal, comprising use of the aforesaid nanoparticles.

Glutathione (GSH) capped CdTe semiconductor quantum dots (QDs) are applied for detecting mercuric ions (Hg(2+)) of trace quantity. The synthesis of GSH-capped CdTe (CdTe@GSH) QDs is cost-efficient and straightforward. We observed that Hg(2+) can quantitatively quench the fluorescence of CdTe@GSH QDs and further induce the slight redshift of emission peaks due to the quantum confinement effect. Detailed studies by spectroscopy, dynamic light scattering (DLS), and electrospray ionization mass spectrometry (ESI-MS) demonstrated that the competitive Hg(2+) binding with GSH makes the surface of CdTe QDs exposed, results in gradual aggregation, and quantitatively changes the photophysical properties of QDs. The whole procedure for detecting Hg(2+) by this protocol took less than 10 min. The experimental limit of detection (LOD) of Hg(2+) can be as low as 5 nM using CdTe@GSH with a low concentration (0.5 nM) because of the excellent fluorescent properties of QDs. This strategy may become a promising means to simply detect Hg(2+) in water with high sensitivity.

The successful and explosive development of nanotechnology is significantly impacting the fields of biology and medicine. Among the spectacular developments of nanobiotechnology, interest has grown in the use of nanomaterials as nanoprobes for bioanalysis and diagnosis. Herein, we review state-of-the-art nanomaterial-based probes and discuss their applications in in vitro diagnostics (IVD) and challenges in bringing these fields together. Major classes of nanoprobes include quantum dots (QDs), plasmonic nanoparticles, magnetic nanoparticles, nanotubes, nanowires, and multifunctional nanomaterials. With the advantages of high volume/surface ratio, surface tailorability, multifunctionality, and intrinsic properties, nanoprobes have tremendous applications in the areas of biomarker discovery, diagnostics of infectious diseases, and cancer detection. The distinguishing features of nanoprobes for in vitro use, such as harmlessness, ultrasensitivity, multiplicity, and point-of-care use, will bring a bright future of nanodiagnosis.

We combined silver and iron oxide nanoparticles to make unique Ag@Fe2O3 yolk–shell multifunctional nanoparticles by the Kirkendall effect. After the surface functionalization using glucose, the Ag@Fe2O3–Glu conjugates exhibited both high capture efficiency of bacteria and potent antibacterial activity. The Ag@Fe2O3 yolk–shell nanostructures may offer a unique multifunctional platform for simultaneous rapid detection and capture of bacteria and safe detoxification treatment.