A Dual-Emission Nanohybrid of Gold Nanoclusters and Carbon Dots for Ratiometric Fluorescence Detection of Reactive Oxygen Species and Glucose.

Detecting reactive oxygen species (ROS) is critical for understanding the mechanisms of diseases. In this work, a convenient ratiometric fluorescent method for determination of ROS was developed basing on a nontoxic nanohybrid system which was constructed by carbon dots (CDs) and gold nanoclusters (Au NCs). The combination was prepared easily basing on self-assembly without any complex process, achieving maximum reservation of the two fluorescent properties. Thus the limit of detection (LOD) for hydrogen peroxide (H2O2) and hypochlorite (ClO-) was lower down to 0.1 µM after the experimental conditions were optimized. Being built to reflect H2O2, the test paper provided a method of convenient visual detection with double fluorescence of CDs/Au NCs. Furthermore, the biosensor was proven to be suitable for the detection of H2O2 and glucose (Glu) in human serum examples. The proportion of CDs and Au NCs was adjusted optionally to different color, while keeping the nanohybrid in high physiological stability and excellent biocompatibility. The excellent performance of this ratiometric biosensor is expected to facilitate further development of rapid and high-throughput detection of ROS.

Fabrication of Carbohydrate-Conjugated Fingerprintlike Mesoporous Silica Net for the Targeted Capture of Bacteria.

Herein, a rapid, straightforward, reliable, and low-cost strategy for targeted capture and detection of bacteria using carbohydrate-conjugated mesoporous silica structure was developed. Fingerprint-like mesoporous silica net (FMSN) with well-defined three-dimensional architecture and ordered morphology was first facilely synthesized by the aid of tetrabutylammonium iodine (TBAI) as cotemplates with cetyltrimethylammonium bromide (CTAB). When conjugated with maltoheptaose as targeting moiety, FMSN showed efficient and selective capturing capability of Staphylococcus epidermidis. This new and unique platform for capturing S. epidermidis is fast (within 18 min), high efficiency (greater than 98.6% from 1 × 103 CFU/mL to 1 × 108 CFU/mL), specific (compared to M. smegmatis mc2 155), and reusable (6 cycles).

BSA Protein-Mediated Synthesis of Hollow Mesoporous Silica Nanotubes, and Their Carbohydrate Conjugates for Targeting Cancer Cells and Detecting Mycobacteria.

A straightforward method was developed to synthesize hollow mesoporous silica nanotubes (HMSNTs) using bovine serum protein (BSA) as the protective coating and phosphate buffered saline (PBS) as the etching agent at room temperature. Galactose-grafted HMSNTs significantly reduced phagocytosis by macrophages, and enhanced cellular uptake by A549 cells via caveolae-mediated uptake pathway. Trehalose-conjugated HMSNTs interacted strongly with mycobacteria, showing the linear detection range from 1 × 104 to 1 × 108 bacteria/mL and the detection limit of 1 × 103 bacteria/mL. In all cases, the hollow nanotube structure showed higher cellular uptake, bacterial binding, and detection efficiency than their spherical counterpart.

One-Pot Synthesis of Fe3O4@PS@P(AEMH-FITC) Magnetic Fluorescent Nanocomposites for Bimodal Imaging.

Magnetic fluorescent nanocomposites have attracted much attention because of their merging magnetic and fluorescent properties for biomedical application. However, the procedure of synthesis of magnetic fluorescent nanocomposites is always complicated. In addition, the properties of fluorescent component could be easily influenced by magnetic component, retaining both of the magnetic and fluorescent properties into one single nanoparticle considered to be a significant challenge. Herein, we report one-pot method to synthesize multifunctional magnetic fluorescent Fe3O4@PS@P(AEMH-FITC) nanocomposites for bimodal imaging. The asprepared Fe3O4@PS@P(AEMH-FITC) nanocomposites with well-define spherical core/shell structure were stable properties. Moreover, the Fe3O4@PS@P(AEMH-FITC) nanocomposites displayed efficient fluorescent and magnetic properties, respectively. Meanwhile, the magnetic resonance imaging (MRI) and HePG2 cancer cell fluorescent images experiment results suggested that Fe3O4@PS@P(AEMH-FITC) nanocomposites could be used as MRI contrast agents and Fluorescence Imaging (FLI) agents for bioimaging application. Our investigation paves a facile avenue for synthesized magnetic fluorescent nanostructures with well biocompatibility for potential bioimaging application in MRI and FLI.

Shape matters when engineering mesoporous silica-based nanomedicines.

Mesoporous silica nanomaterials have been successfully employed in the development of novel carriers for drug delivery. Numerous studies have been reported on engineering mesoporous silica-based carriers for drug loading, release, cellular uptake, and biocompatibility. A number of design parameters that govern the in vitro and in vivo performance of the carriers, including particle diameter, surface chemistry, and pore size, have been tuned to optimize nanomedicine efficacy. However, particle shape, which may generate a high impact on nanomedicine performance, has still not been thoroughly investigated. This is probably due to the limited availability of strategies and techniques to produce non-spherical mesoporous silica nanomaterials. Recent breakthroughs in controlling the particle shape of mesoporous silica nanomaterials have confirmed the important roles of shape on nanomedicine development. This review article introduces various fabrication methods for non-spherical mesoporous silica nanomaterials, including rod, ellipsoid, film, platelet/sheet, and cube, and the roles of particle shape in nanomedicine applications.

One-pot synthesis of active copper-containing carbon dots with laccase-like activities.

Herein, an effective strategy for designing a new type of nanozyme, blue fluorescent laccase mimics, is reported. Active copper-containing carbon dots (Cu-CDs) were synthesized through a simple, nontoxic and one-pot hydrothermal method, which showed favorable photoluminescence properties and good photostability under high-salt conditions or in a broad pH range (3.0-13.5). The Cu-CDs possessed intrinsic laccase-like activities and could catalyze the oxidation of the laccase substrate p-phenylenediamine (PPD) to produce a typical color change from colorless to brown. Poly(methacrylic acid sodium salt) (PMAA) not only was used as the carbon source and reducing agent, but also provided carboxyl groups to assist flocculation between Cu-CDs and polyacrylamide, which facilitated the removal of PPD. Importantly, the intrinsic fluorescence of the as-prepared Cu-CDs could indicate the presence of hydroquinone, one of the substrates of laccases, based on laccase mimics and fluorescence quenching.

Fatigue damage to pig erythrocytes during repeated swelling and shrinkage.

During the removal of cryoprotectants from cryopreserved-thawed blood with the dialysis-based or dilution-filtration method, due to the change in the extracellular osmolality, erythrocytes usually undergo repeated swelling and shrinkage. However, the erythrocyte fatigue damage induced by this repeated volume change has not yet been studied. In this work, by successively loading hypotonic and hypertonic solutions, we mimicked the repeated swelling and shrinkage of pig erythrocytes and then examined the effect of the number of cycle loops on the steady-state volume and the mortality of the pig erythrocytes. The results suggest that because of cell leakage in the swelling process, the steady-state volume of the pig erythrocytes after one cycle is smaller than the volume before the cycle, even though the cell performs a self-protective regulatory procedure. If the number of cycle loops is increased, the repeated swelling and shrinkage will cause a continuous decrease in the steady-state volume, and the ability of the pig erythrocytes to resist osmotic damage will decrease; as a result, the mortality of the pig erythrocytes increases as the number of cycle loops increases. The viability of the cells is also affected by the hypotonic and isotonic processing times: a short processing time may contribute to a decrease in the mortality of the pig erythrocytes. This work is of significance to optimizing the process of removing cryoprotectants.

Encapsulating Ionic Liquid and Fe3O4 Nanoparticles in Gelatin Microcapsules as Microwave Susceptible Agent for MR Imaging-guided Tumor Thermotherapy.

The combination of therapies and monitoring the treatment process has become a new concept in cancer therapy. Herein, gelatin-based microcapsules have been first reported to be used as microwave (MW) susceptible agent and magnetic resonance (MR) imaging contrast agent for cancer MW thermotherapy. Using the simple coacervation methods, ionic liquid (IL) and Fe3O4 nanoparticles (NPs) were wrapped in microcapsules, and these microcapsules showed good heating efficacy in vitro under MW irradiation. The results of cell tests indicated that gelatin/IL@Fe3O4 microcapsules possessed excellent compatibility in physiological environments, and they could effectively kill cancer cells with exposure to MW. The ICR mice bearing H22 tumors treated with gelatin/IL@Fe3O4 microcapsules were obtained an outstanding MW thermotherapy efficacy with 100% tumor elimination under ultralow density irradiation (1.8 W/cm(2), 450 MHz). In addition, the applicability of the microcapsules as an efficient contrast agent for MR imaging in vivo was evident. Therefore, these multifunctional microcapsules have a great potential for MR imaging-guided MW thermotherapy.

Gelatin microcapsules for enhanced microwave tumor hyperthermia.

Local and rapid heating by microwave (MW) irradiation is important in the clinical treatment of tumors using hyperthermia. We report here a new thermo-seed technique for the highly efficient MW irradiation ablation of tumors in vivo based on gelatin microcapsules. We achieved 100% tumor elimination in a mouse model at an ultralow power of 1.8 W without any side-effects. The results of MTT assays, a hemolysis test and the histological staining of organs indicated that the gelatin microcapsules showed excellent compatibility with the physiological environment. A possible mechanism is proposed for MW hyperthermia using gelatin microcapsules. We also used gelatin microcapsules capped with CdTe quantum dots for in vivo optical imaging. Our study suggests that these microcapsules may have potential applications in imaging-guided cancer treatment.

A smart all-in-one theranostic platform for CT imaging guided tumor microwave thermotherapy based on IL@ZrO2 nanoparticles.

This study develops a simple hollow ZrO2 nanostructure as a carrier to encapsulate ionic liquid (IL), which integrates the CT imaging function of the ZrO2 shell and the microwave susceptibility function of the IL core. The simple nanostructure can be used as a multifunctional theranostic agent via combining diagnostic and therapeutic modalities into one "package". Based on the microwave susceptibility properties, the tumor inhibiting ratio can be over 90% in mice models after one-time thermal therapy upon microwave irradiation. In vitro and in vivo imaging results prove the potential of CT imaging application for real-time monitoring of biodistribution and metabolic processes, and assessing therapeutic outcomes. To our best knowledge, our study is the first example to achieve CT imaging and microwave thermal therapy simultaneously through a simple nanostructure. We anticipate that the simple IL@ZrO2 nanostructure may build a useful platform for the clinical imaging guided therapy of tumors.

Fast synthesis of fluorescent SiO2@CdTe nanoparticles with reusability in detection of H2O2.

In this study, highly fluorescent core/shell SiO2@CdTe nanoparticles (NPs) were synthesized conveniently and efficiently via a hydrothermal method. The as-prepared SiO2@CdTe NPs were uniform with good fluorescence preservation. The SiO2@CdTe NPs could be used for the rapid detection of H2O2 with good sensitivity within several minutes. Excellent linear relationships existed between the quenching degrees of the SiO2@CdTe NPs and the concentration of H2O2 in the range of 0.005 mM to 0.1 mM. The limit of detection (LOD) for H2O2 was 10 nM. Furthermore, it was proved that SiO2@CdTe NPs could be used repeatedly for H2O2 detection due to their easy separation, which is an important feature. The excellent performance of SiO2@CdTe NPs should facilitate their applications in chemistry or biology for detection of H2O2.

A sensitive biosensor for the fluorescence detection of the acetylcholinesterase reaction system based on carbon dots.

The carbon dots (C-dots) with high fluorescence quantum yield were prepared using hydrothermal method. C-dots have been adopted as probes for the fluorescence turn-off detection of H2O2 based on the special sensibility for the hydroxyl radical. And then the biosensors for the detection of substrate and enzymes activities were established in the acetylcholinesterase reaction system, which were related to the production of H2O2. Specifically, the proposed fluorescent biosensor was successfully applied to detect the concentration of choline (in the range from 0.025 to 50 µM) and acetylcholine (in the range from 0.050 to 50 µM), and the activity of choline oxidase (in the range from 1 to 75 U/L) and acetylcholinesterase (1 to 80 U/L). These results showed a sensitive, universal, nontoxic and eco-friendly detecting technique has been developed.

Synthesis of ultra-stable fluorescent carbon dots from polyvinylpyrrolidone and their application in the detection of hydroxyl radicals.

Highly biocompatible and highly photostable fluorescent carbon dots (C dots) were obtained through a simple and nontoxic one-pot hydrothermal method. Polyvinylpyrrolidone, a common and low-cost biocompatibility reagent, was used as the only carbon source for the first time. The resulting water-soluble C dots showed a quantum yield of up to 23.58% with low cytotoxicity, favorable photoluminescent properties, and good photostability. Importantly, the fluorescence intensities of the C dots were quite stable in high-salt conditions and over a broad pH range (3.0-10.5). The as-prepared C dots have been demonstrated to be an excellent probe for hydroxyl radicals sensing based on the fluorescence quenching with great sensitivity and specificity. This opens up a new application field for C dots.

Icosahedral gold-platinum alloy nanocrystals in hollow silica: a highly active and stable catalyst for Ullmann reactions.

Icosahedral Au-Pt alloy nanocrystals are prepared in porous hollow silica nanospheres via a hydrothermal method without using capping agents. These nanoparticles with unique shape and structure exhibit excellent catalytic activity and stability in Ullmann reactions.

Shape-mediated biological effects of mesoporous silica nanoparticles.

For biomedical applications, mesoporous silica nanoparticles (MSNs)-based theranostic agents have shown to be a promising alternative. Rational design of particulate systems should consider, beside the physicochemical properties of particle size and surface chemistry, shape features as aspect ratio (AR) and morphology. Recent advances of fabrication technologies for manufacturing different shaped MSNs and evaluation means of its in vitro and in vivo biological performance provide new aspects and wisdom in nanomedicine development. In this review, we discussed the recent progress in the preparation of different shaped MSNs and the evaluation of shape-mediated biological effects. Firstly, we provide an overview of preparation strategies for fabricating MSNs with different aspect ratios and different morphologies, including hollow/rattle MSNs, multishell MSNs, and mesoporous silica nanocomposites. We then highlight the aspect ratio- and morphology-mediated biological effects of MSNs respectively. For AR-mediated biological effects of MSNs, we put our focus in the particle ARs effect on cellular uptake, biocompatibility, and drug delivery. For morphology-mediated biological effects of MSNs, we emphasize on how particle shapes could affect tumor therapy. Finally, for application considerations, we conclude with our personal perspectives on the directions in which future studies in this field might be placed.

An eco-friendly, simple, and sensitive fluorescence biosensor for the detection of choline and acetylcholine based on C-dots and the Fenton reaction.

A simple and novel method is proposed for the preparation of Carbon dots (C-dots) with excellent properties. We firstly demonstrated that the fluorescence of C-dots decreased apparently in the presence of H2O2 and Fe(2+). Based on the this finding, C-dots are successfully adopted as probes for the detection of H2O2. After the experimental conditions are optimized, the limit of detection (LOD) for H2O2 is found to be 0.1 µM. Furthermore, we established an eco-friendly, simple and sensitive biosensor for the detection of choline and acetylcholine (ACh) based on the detection of H2O2 using C-dots as probes. The detection limit for choline is 0.1 µM and the linear range is 0.1-40 µM. The detection limit for ACh is found to be 0.5 µM and the linear range is 0.5-60 µM. The excellent performance of the proposed biosensor shows that this method possesses the potential for practical application.

Smaller silica nanorattles reabsorbed by intestinal aggravate multiple organs damage.

Recent advances in design and controllable synthesis of rattle-type silica nanoparticles have led to a dramatic expansion of their potential drug delivery application. However, the relationship between physico-chemical parameters and bio-effects of silica nanoparticles is still unclear. In the present study, we investigated the effect of particle size on acute toxicity caused by intravenously administered silica nanorattles (SNs) in vivo. Above all, we found that SNs with smaller size may have higher toxicity potency. SNs sized 60 nm but not the others induced multi-organs structural damages, such as necrosis, congestion and haemorrhage. Interestingly, the different feeding mode after the fasted treatment induced the divarication of toxicity of 60 nm SNs. Smaller particles induced mortality even at 100 mg/kg dose injection when mice fasted for 12 hours and instantly replenish food. But no death had happened when mice received food with gradually recovery after the same treatment. The results indicate that smaller SNs drained into the intestinal tract with the bile liquids from liver may be reabsorbed into the blood through the impaired intestinal barriers and induce worse re-injure. These findings may provide useful information for the further toxicity and biodistribution research of nanoparticles.

Sensitive and selective detection of Hg2+ and Cu2+ ions by fluorescent Ag nanoclusters synthesized via a hydrothermal method.

An easily prepared fluorescent Ag nanoclusters (Ag NCs) probe for the sensitive and selective detection of Hg(2+) and Cu(2+) ions was developed here. The Ag NCs were synthesized by using polymethacrylic acid sodium salt as a template via a convenient hydrothermal process. The as-prepared fluorescent Ag NCs were monodispersed, uniform and less than 2 nm in diameter, and can be quenched in the presence of mercury (Hg(2+)) or copper (Cu(2+)) ions. Excellent linear relationships existed between the quenching degree of the Ag NCs and the concentrations of Hg(2+) or Cu(2+) ions in the range of 10 nM to 20 µM or 10 nM to 30 µM, respectively. By using ethylenediaminetetraacetate (EDTA) as the masking agent of Cu(2+), Hg(2+) was exclusively detected in coexistence with Cu(2+) with high sensitivity (LOD = 10 nM), which also provided a reusable detection method for Cu(2+). Furthermore, the different quenching phenomena caused by the two metals ions such as changes in visible colour, shifts of UV absorbance peaks and changes in size of Ag NCs make it easy to distinguish between them. Therefore the easily synthesized fluorescent Ag NCs may have great potential as Hg(2+) and Cu(2+) ions sensors.