MnO2 nanosheet quenched thulium doped photon-up conversion luminescent immunoprobe for the 'turn-on' detection of cardiac troponin T.

A "turn-on" photon up conversion nano couple based on NaYF4: Yb, Tm UCNPs quenched with MnO2 nanosheet was developed for the rapid and selective detection of cTnT. Herein, MnO2 nanosheet hold on the surface of Antibody cTnT (Ab-cTnT) conjugated blue emitting up conversion nanoprobe (λem at 475 nm), which leads to quenching of fluorescence due to energy transfer from photon up conversion nanoparticles to MnO2 nanosheets. On introducing cTnT antigen to the system, the energy transfer process is hindered due to strong antigen -antibody interface on the surface. This in turn, influences the nano-couples positions and effectively separates up conversion nanoprobe from MnO2 nanosheets surface resulting in restriction to energy transfer process enabling fluorescence recovery. The developed probe shows a linear response towards cTnT in the range of 0.16-2.77 ng/mL with a Limit of Detection (LoD) of 0.025 ng/mL. The practical feasibility of the nanoprobe is performed with possible coexisting biomolecules. Biological study in human blood serum samples exhibited sufficient recovery percentage in the range of 92-103 % is obtained.

Self-assembled ratiometric sensor for specific detection of hypoxia in living cells based on lanthanide-doped upconversion nanoparticles and gold nanoparticles.

We describes the development of a self-assembled nanoprobe for ratiometric sensing of hypoxia in living cells. The probe, UC-AuNPs, is composed of azo-functionalized upconversion nanoparticles (azo-UCNPs) and gold nanoparticles functionalized withß-cyclodextrin (CD-AuNPs). Under hypoxic conditions, reductases reduce azo derivatives on the UCNPs, leading to detachment of the CD-AuNPs and subsequent fluorescence recovery of the green emission. The ratiometric measurement incorporated into the strategy reduces the impact of external factors and improves sensitivity of the probe. The use of NIR excitation effectively minimizes interference from strong luminescence backgrounds in biosystems. The UC-AuNPs nanoprobe is able to effectively sense and monitor hypoxia conditions in living cells and has the potential to distinguish hypoxia-related diseases from healthy tissue, making it a valuable tool for early clinical diagnosis.

NIR-II nano fluorescence image guided hepatic carcinoma resection on cirrhotic patient.

Precise resection of hepatic carcinoma (HCC) remains challenging for cirrhotic patients. Cirrhosis not only effects intraoperative palpation, but can also cause severe false-positive problems to indocyanine green (ICG) fluorescence imaging. Herein, we report the application of a nano-scale probe IgG-IRDye800CW to achieve precise HCC resection from cirrhotic liver. A 66-year-old male patient with liver cancer received intravenous injection of IgG-IRDye800CW (10 mg) 6 days prior to surgery, and none adverse effects were observed. During the operation, the HCC lesion in the right liver lobe was specifically detected on the near-infrared window II (NIR-II) fluorescence images. The high-contrast NIR-II fluorescence delineated a clear margin to improve surgical precision. These clinical observations showed high safety and feasibility of applying IgG-IRDye800CW NIR-II fluorescence imaging to guide hepatic surgery and minimize hepatic function damage.

Colorimetric nano-beacon and magnetic separation-based rapid and visual assay for gram-negative bacteria.

Food-borne diseases caused by pathogenic bacteria are one of the serious factors affecting human health. However, the most commonly used detection methods for pathogenic bacteria not only require expensive instruments, but also take a long time due to the complicated and cumbersome detection process. Therefore, the development of a fast, simple, and low-cost detection method for pathogenic bacteria is crucial for food safety and human health. In this work, based on the high binding ability of antimicrobial peptide (AMP) and polymyxin B (PMB) to bacteria, combined with magnetic separation technology, a new enzyme-free colorimetric strategy was constructed to achieve visual detection of Gram-negative bacteria in complex samples. The sensor system was divided into the following two parts: a colorimetric signal amplification nanoprobe, which was modified with AMP to enable effective binding of the colorimetric probe to the surface of bacteria, and a PMB-modified magnetic nanobead (MNB), which was used as the capture and enrichment unit of Gram-negative bacteria, as a result of which PMB could effectively distinguish Gram-negative bacteria from Gram-positive bacteria. Under optimized conditions, the detection limit of the method for Gram-negative bacteria (e.g. E. coli (G-)) was as low as 10 CFU/mL, and it was successfully applied to complex real samples. In addition, the developed colorimetric sensor offered advantages, such as fast response, less time consumption, high sensitivity, and low cost. It can be expected to become a new diagnostic tool for on-site detection of pathogenic bacteria in remote areas.

Fluorescent carbon dots as selective nano probe for determination of diacerein in presence of co-formulated drugs.

In this work, a new and simple carbon dots (CDs) based fluorescent probe was introduced for selective determination of diacerein (DIA) in presence of two co-formulated drugs. This highly fluorescent sensor was constructed using chitosan as a carbon and nitrogen source by single step carbonization. The constructed probe is based on the inner filter effect (IFE), in which DIA serves as a strong absorber, influencing the excitation of the fluorescer (CDs). This overlap leads to quenching of CDs fluorescence upon increasing DIA concentration within the range of 2.5-17.5 µg/mL with mean % recovery reached to 99.7 ± 0.7. The performance of the constructed sensor had been validated according to the ICH guidelines and the results revealed that it is precise and accurate. Moreover, it has many advantages such as simplicity, saving time and good selectivity for the determination of DIA as a minor component in presence of co-formulated drugs in its tablet dosage form.

A near-infrared light triggered fluormetric biosensor for sensitive detection of acetylcholinesterase activity based on NaErF4: 0.5 % Ho3+@NaYF4 upconversion nano-probe.

Acetylcholinesterase (AChE), as an important neurotransmitter, is widely present in the peripheral and central nervous systems. The aberrant expression of AChE could cause diverse neurodegenerative diseases. Herein, we developed a facile and interference-free fluorimetric biosensing platform for highly sensitive AChE activity determination based on a NaErF4: 0.5 % Ho3+@NaYF4 nano-probe. This nano-probe exhibits a unique property of emitting bright monochromic red (650 nm) upconversion (UC) emission under multiband (~808, ~980, and ~1530 nm) near-infrared (NIR) excitations. The principle of this detection relies on the quenching of the strong monochromic red UC emission by oxidization products of 3,3',5,5'-tetramethylbenzidine generated through AChE-modulated cascade reactions. This system shows a great sensing performance with a detection limit (LOD) of 0.0019 mU mL- 1 for AChE, as well as good specificity and stability. Furthermore, we validated the potential of the nano-probe in biological samples by determination of AChE in whole blood with a LOD of 0.0027 mU mL-1, indicating the potential application of our proposed platform for monitoring the progression of AChE-related disease.

Development of Ag nanoparticle-carbon quantum dot nanocomplex as fluorescence sensor for determination of gemcitabine.

Gemcitabine hydrochloride is an established chemotherapeutic agent in several solid tumors. In spite of outstanding therapeutic efficacy, there are some serious fetal side effects with gemcitabine in higher concentrations which necessitate developing a sensitive sensor for its quantification. Herein, a fluorescent metal-nanoparticles conjugated carbon quantum dot (MN-CQD) was prepared by a mixture of citric acid/ammonia sulfate and different metals using hydrothermal method. Based on the primary experiments, the efficiency of Ag nanoparticle-CQDs for gemcitabine determination was found to be much better than others. The AgNp-CQDs fluorescence was quenched by gemcitabine anticancer drug via photo-induced charge transfer which renders the system into fluorescence "OFF" status. Under the experimental conditions, the linear range of detection was 0.003-0.1 µM in an aqueous solution with a correlation coefficient of 0.96 and a limit of detection equal to 0.002 µM. The relative standard deviation (RSD) for gemcitabine determination was 3.4% (n = 3). Finally, after optimizing the conditions, the concentration of analyte was determined in real samples including human plasma and urine. These results confirm that the as prepared fluorescence based nanosensor can be used for sensitive quantification of gemcitabine in real samples.

A label-free nano-probe for sequential and quantitative determination of Cr(VI) and ascorbic acid in real samples based on S and N dual-doped carbon dots.

A fluorescent sulfur and nitrogen dual-doped carbon dots (S,N-CDs) was prepared by a simple and one-step acid-base neutralization and exothermic carbonization method. Hexavalent chromium (Cr(VI)) could effectively quench the fluorescence of S,N-CDs based on inner filter effect (IFE) and dynamic quenching, whereas ascorbic acid (AA) could recover the fluorescence of S,N-CDs/Cr(VI) because of IFE weakening. So an "on-off-on" and label-free nano-probe consecutive determination of Cr(VI) and AA was constructed. This nano-probe system demonstrated excellent selectivity and sensitivity to Cr(VI) and AA with linear range of 0.065-198 µmol/L (3.38-10,296 µg/L) and 6.6-892 µmol/L (1.16-157 mg/L), respectively. Meanwhile, the as-prepared S,N-CDs possess low toxicity and could be used for multi-color cell imaging in SMMC 7721 cells. More importantly, this nano-probe was successfully employed for detection of Cr(VI) in tap water and AA in food samples. In view of its simple detection condition, rapid response, wide linear range, low detection limit and inexpensive instrument, the as-constructed nano-probe system could have a wide range of potential application, including water quality monitoring and evaluation, food inspection and testing and biomedical analysis.

Determination of Verapamil HCl in Pharmaceutical Preparations by a Fluorescent Nano Probe Based on CdTe/CdS/ZnS Quantum Dots.

An analytical technique based on fluorescence quenching of CdTe/CdS/ZnS quantum dots (QDs) was developed to quantify verapamil in commercially available preparations. Various reaction parameters were optimized and the method developed was validated. One way analysis of variance (ANOVA) and post hoc tests at a 5% significance level were performed to justify the significance of the variation in observations. The linear range of the verapamil concentration was 0.25-5 µg/mL while the limit of detection was 20 µg/mL. Recovery and relative standard deviations were not more than ±10% of the actual amount and <5.9%, respectively. Foreign materials, common metal ions and pharmaceutical excipients of dosage forms caused little interference. To verify the application of the analytical method, the quantity of verapamil in commercially available dosage forms was measured. Verapamil content in the tablets and injections was not more than ±10% of the stated amount and it conformed to the specifications of both the British and the United States pharmacopoeias. In the case of statistical analysis, p-value was <0.05 in almost all levels of all parameters except for the optimized level of system. It can be concluded from the results that the designed method is simple, reliable, cost effective, selective, rapid and sensitive enough to be used for quantitative measurement of the verapamil HCl in dosage forms for quality control purposes.

Dual nano-sized contrast agents in PET/MRI: a systematic review.

Nowadays molecular imaging plays a vital role in achieving a successful targeted and personalized treatment. Hence, the approach of combining two or more medical imaging modalities was developed. The objective of this review is to systematically compare recent dual contrast agents in Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) and in some cases Single photon emission computed tomography (SPECT)/MRI in terms of some their characteristics, such as tumor uptake, and reticuloendothelial system uptake (especially liver) and their relaxivity rates for early detection of primary cancer tumor. To the best of our knowledge, this is the first systematic and integrated overview of this field. Two reviewers individually directed the systematic review search using PubMed, MEDLINE and Google Scholar. Two other reviewers directed quality assessment, using the criteria checklist from the CAMARADES (Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies) tool, and differences were resolved by consensus. After reviewing all 49 studies, we concluded that a size range of 20-200 nm can be used for molecular imaging, although it is better to try to achieve as small a size as it is possible. Also, small nanoparticles with a hydrophilic coating and positive charge are suitable as a T2 contrast agent. According to our selected data, the most successful dual probes in terms of high targeting were with an average size of 40 nm, PEGylated using peptides as a biomarker and radiolabeled with copper 64 and gallium 68. Copyright © 2017 John Wiley & Sons, Ltd.

Hybrid electron microscopy-FRET imaging localizes the dynamical C-terminus of Tfg2 in RNA polymerase II-TFIIF with nanometer precision.

TFIIF-a general transcription factor comprising two conserved subunits can associate with RNA polymerase II (RNAPII) tightly to regulate the synthesis of messenger RNA in eukaryotes. Herein, a hybrid method that combines electron microscopy (EM) and Förster resonance energy transfer (FRET) is described and used to localize the C-terminus of the second TFIIF subunit (Tfg2) in the architecture of RNAPII-TFIIF. In the first stage, a poly-histidine tag appended to the Tfg2 C-terminus was labeled with nickel-NTA nanogold and a seven-step single particle EM protocol was devised to obtain the region accessible by the nanogold in 3D, suggesting the Tfg2 C-terminus is proximal to the clamp of RNAPII. Next, the C-termini of the Rpb2 and the Rpb4 subunits of RNAPII, adjacent to the clamp, were selected for placing FRET satellites to enable the nano-positioning (NP) analysis, by which the localization precision was improved such that the Tfg2 C-terminus was found to dwell on the clamp ridge but could move to the clamp top during transcription. Because the tag receptive to the EM or FRET probes can be readily introduced to any protein subunit, this hybrid approach is generally applicable to complement cryo-EM study of many protein complexes to nanometer precision.