Core-shell hybrid upconversion nanoparticles carrying stable nitroxide radicals as potential multifunctional nanoprobes for upconversion luminescence and magnetic resonance dual-modality imaging.

Nitroxide radicals, such as 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO) and its derivatives, have recently been used as contrast agents for magnetic resonance imaging (MRI) and electron paramagnetic resonance imaging (EPRI). However, their rapid one-electron bioreduction to diamagnetic N-hydroxy species when administered intravenously has limited their use in in vivo applications. In this article, a new approach of silica coating for carrying stable radicals was proposed. A 4-carboxyl-TEMPO nitroxide radical was covalently linked with 3-aminopropyl-trimethoxysilane to produce a silanizing TEMPO radical. Utilizing a facile reaction based on the copolymerization of silanizing TEMPO radicals with tetraethyl orthosilicate in reverse microemulsion, a TEMPO radicals doped SiO2 nanostructure was synthesized and coated on the surface of NaYF4:Yb,Er/NaYF4 upconversion nanoparticles (UCNPs) to generate a novel multifunctional nanoprobe, PEGylated UCNP@TEMPO@SiO2 for upconversion luminescence (UCL) and magnetic resonance dual-modality imaging. The electron spin resonance (ESR) signals generated by the TEMPO@SiO2 show an enhanced reduction resistance property for a period of time of up to 1 h, even in the presence of 5 mM ascorbic acid. The longitudinal relaxivity of PEGylated UCNPs@TEMPO@SiO2 nanocomposites is about 10 times stronger than that for free TEMPO radicals. The core-shell NaYF4:Yb,Er/NaYF4 UCNPs synthesized by this modified user-friendly one-pot solvothermal strategy show a significant enhancement of UCL emission of up to 60 times more than the core NaYF4:Yb,Er. Furthermore, the PEGylated UCNP@TEMPO@SiO2 nanocomposites were further used as multifunctional nanoprobes to explore their performance in the UCL imaging of living cells and T1-weighted MRI in vitro and in vivo.

Extraordinary modulation of disulfide redox-responsiveness by cooperativity of twin-disulfide bonds.

Disulfide bonds have frequently been incorporated into synthetic materials to promote sensitivity of the systems towards different redox environments. Although many strategies have been developed to rationally tune the stability of disulfide linkers, methods to tune their responsiveness towards different redox environments remain elusive. In this work we have developed and explored a disulfide linker bearing two independent disulfide bonds, referred to as a twin-disulfide linker. We have demonstrated that the twin-disulfide linker displays an ultrahigh stability at lower concentrations of reducing agent or in weakly reducing environments without a significant compromise in the sensitivity of its response to highly reducing environments such as cytoplasm, a feature that is in remarkable contrast to the traditional single disulfide bonds. Such an extraordinary responsiveness arises from the cooperativity of the twin-disulfide bonds, which should be of particular interest for applications such as controlled drug delivery and sensing, because relatively large differences in disulfide stability in different redox environments is desired in these applications.

Exploring and exploiting dynamic noncovalent chemistry for effective surface modification of nanoscale metal-organic frameworks.

Surface properties determine, to a great extent, the biologically relevant functions of various kinds of nanosized materials. Although the modification of the surface of traditional inorganic or polymeric nanoparticles can be routinely achieved through covalent or noncovalent manner or both, the surface modification of nanoscale metal-organic frameworks (nano-MOFs) is extremely challenging because of their rapid degradation in aqueous environments. In this work, we systematically studied the synergistic and dynamic noncovalent interactions between fluorescent probes and iron(III) carboxylate nano-MOFs (i.e., MIL-101-NH2 (Fe), one of the most prevalent MOFs used in drug delivery and imaging). We further examined the interplay between the surface binding of fluorescent probes and the degradation of MIL-101-NH2 (Fe) in aqueous medium. It was demonstrated that the surface binding of probes is not only of high affinity but also dynamic and nonsheddable, even during the degradation, a feature that is essentially different from the covalent conjugation. Subsequently, we developed a unique and straightforward strategy for the surface modification of MIL-101-NH2 (Fe) with polymer by exploiting the synergy of noncovalent interactions between functionalized copolymers and MIL-101-NH2 (Fe). We demonstrated that the binding of polymers onto MIL-101-NH2 (Fe) surface was very effective in aqueous solution and surprisingly nonsheddable during the process of degradation. Surface polymers can creep on the surface of MIL-101-NH2 (Fe), in a dynamic and real-time manner, to the new sites formed immediately after the degradation. In addition, the stability of MIL-101-NH2 (Fe) particles in aqueous environments can be improved to some extent by the surface polymer coating. The results presented herein constitute an important innovation for surface engineering of nano-MOFs, which would benefit the application of nano-MOFs as delivery systems in aqueous systems.

Quantum dot-Eu3+ conjugate as a luminescence turn-on sensor for ultrasensitive detection of nucleoside triphosphates.

We report a conjugate of thioglycolic acid (TGA) capped CdTe quantum dot and Eu(3+) ion (TGA-CdTe QD-Eu(3+)) that can be used as an ultrasensitive luminescence turn-on sensor for nucleoside triphosphates (NTPs). The TGA-CdTe QD-Eu(3+) conjugate is a weakly luminescent species as a result of the strong quenching effect of Eu(3+) ion on the luminescence of TGA-CdTe QDs. The conjugate's luminescence can be readily restored by its reaction with adenosine triphosphate (ATP) and other NTPs, and thus gives an ultrasensitive detection of NTPs, with a detection limit of 2 nM. The sensing mechanism has also been explored, and the effective quenching of TGA-CdTe QDs emission by Eu(3+) ions has been attributed to photoinduced electron transfer (PET). ATP, as the representative of NTPs, can remove Eu(3+) from the surface of TGA-CdTe QDs, leading to restoration of the TGA-CdTe QDs luminescence.

Ultrasensitive detection of phenolic compounds based on a spin-labeled luminescent lanthanide complex.

Herein we propose a novel method for ultrasensitive detection of phenolic compounds. This method was developed based on a spin-labeled terbium complex Tb(3+)/cs124-DTPA-TEMPO (1). This spin-labeled terbium complex is a weakly luminescent compound and shows strong off-on luminescent response to phenolic compounds in the presence of horseradish peroxidase (HRP), glutathione (GSH) and hydrogen peroxide. The analyte recognition and signaling mechanism are discussed and the factors affecting the off-on luminescence have been explored. Detection limits of 1.1 nM for phenol, 1.1 nM for resorcine, 0.6 nM for m-cresol, 3 nM for p-cresol, and 0.5 nM for 2,4-dichlorophenol were obtained, respectively. The practicability of the proposed method has been tested in detection of the concentration of spiked nearshore seawaters, and recoveries of 77.4-80.4% with relative standard deviations (RSDs) of 1.0-2.2% were obtained.

A highly sensitive and selective antioxidant probe based on a bi-modally functionalized conjugated polyelectrolyte.

A new water-soluble anionic conjugated polyelectrolyte with a nitroxide radical covalently linked to the sulfonated poly(phenylene ethynylene) backbone (PPE-SO(3)) is reported. This radical-functionalized PPE-SO(3) (RF-PPE-SO(3)) demonstrates fluorescence and electron spin resonance (ESR) bimodal signaling function and shows sensitive and selective response to antioxidants.

A long-lived luminescence and EPR bimodal lanthanide-based probe for free radicals.

We developed a novel spin-labeled terbium complex Tb(3+)/cs124-DTPA-TEMPO (1) by covalently labeling a nitroxide radical on the terbium complex for monitoring free radicals of various areas. This lanthanide complex probe shows a high EPR signal which resulted from the nitroxide radical moiety, and is weakly luminescent which resulted from the intramolecular quenching effect of the nitroxide radical on sensitised terbium luminescence. The intensity of both the EPR and luminescence can be modulated by eliminating the paramagnetism of the nitroxide radical through recognition of a carbon-centered radical analyte and thus gives a quantification of the analyte. We have preliminarily applied this probe in the luminescent detection of model carbon-centered radicals and hydroxyl radicals (·OH). This probe is water-soluble and contains lanthanide-luminescence properties, favorable for the time-resolved luminescence technique. The investigation of the intramolecular quenching process has showed that the labeled nitroxide radical quenches multiple excited states of the terbium complex, resulting in highly efficient quenching of terbium luminescence. This probe is the first example of intramolecular modulation of lanthanide luminescence by a nitroxide radical.

Facile one-pot synthesis of near-infrared luminescent gold nanoparticles for sensing copper (II).

Novel near-infrared luminescent gold nanoparticles (NIRL-AuNPs) were synthesized by a simple, rapid and one-pot procedure. The driving force for the formation of these NIRL-AuNPs was attributed to the heat-assisted reduction of a gold(I)-thiol complex. These gold nanoparticles were characterized by TEM, DLS, FT-IR and XPS. Luminescence studies indicated that these NIRL-AuNPs exhibited strong emission with peak maximum at 810 nm, microsecond-range photoluminescence lifetime, large Stokes shifts (>400 nm) and stabilities towards photobleaching and chemical oxidation. The sensing application for Cu(2+) ions of these NIRL-AuNPs was demonstrated. These as-synthesized gold nanoparticles will provide a new NIRL nanomaterial for in vitro and in vivo applications.

Ultrasensitive Pb2+ detection based on fluorescence resonance energy transfer (FRET) between quantum dots and gold nanoparticles.

Positively charged CdTe-QDs capped with cysteamine (CA-CdTe-QDs) and negatively charged AuNPs capped with 11-mercaptoundecanoic acid (MUA-AuNPs) have been prepared. They are water-soluble and biocompatible. An assay for the determination of Pb2+ has been proposed based on the modulation in FRET efficiency between QDs and AuNPs in the presence of Pb2+, which inhibits the interaction of the QD-AuNP assembly. This method is easy to operate and with remarkably high sensitivity. Under the optimum conditions, the response is linearly proportional to the concentration of Pb2+ in the range 0.22-4.51 ppm, and the detection limit is found to be 30 ppb of Pb2+ due to the superior fluorescence properties of QDs. The mechanism of this strategy is also discussed.

Fluorescent gold nanoparticles-based fluorescence sensor for Cu2+ ions.

A new fluorescence sensor for the highly selective detection of Cu2+ ion with a detection limit of 3.6 nM based on the aggregation-induced fluorescence quenching of the highly fluorescent glutathione-capped gold nanoparticles is reported.

[Study on ratiometric determination of peroxynitrite and its scavenger based on synchronous fluorescence spectroscopy].

A ratiometric fluorimetry is proposed for the determination of peroxynitrite (ONOO-) and the evaluation of its scavenger based on synchronous fluorescence spectroscopy. L-tyrosine, an intrinsic fluorescent aminoacid, reacts with peroxynitrite and carbon dioxide, yielding a highly fluorescent dimer of tyrosine in pH 8.5 PBS buffer solution. By synchronous fluorescence scanning, both monomer and dimer emission bands of L-tyrosine appeared at 364 and 406 nm, respectively. The ratio of F406/ F364 is quantitatively related to the concentration of peroxynitrite, where F406 represents the intensity of synchronous emission band of dimer and F364 represents that of monomer. The method has been showing merit of being insensitive to the changes in experimental parameters and offers a higher sensitivity and a broader responding linear range of the analyte concentration, compared to fluorimetric method, giving a LOD of 1.84 X 10(-8) mol x L(-1) and a linear range of 1.60 X 10(-7) mol x L(-1)-6.00 X 10(-6) mol x L(-1) for ONOO-, respectively, with a deviation of 2.4% for 1.00 X 10(-6) mol x L(-1) ONOO- (n = 8). A IC50 of 0.065 microg x mL(-1) for mitoxantrone, an antioxidant and anticancer drug, was also obtained. This method has proved to be simple and speedy. It would be easily used in the determination of ONOO- and its scavenger.

Fluorescent core-shell silica nanoparticles as tunable precursors: towards encoding and multifunctional nano-probes.

Core-shell silica nanoparticles comprised of a RuBpy doped silica core and a Pas-DTPA doped silica shell were synthesized and post-functionalized with an encoding fluorescence combination and multiplex imaging function.

Screening of tetracycline residues in fish muscles by CCD camera-based solid-surface fluorescence.

A methodology for the screening of tetracyclines (TCs), including tetracycline (TC), oxytetracycline (OTC), and chlorotetracycline (CTC), in different fish muscle matrices has been proposed. This method was based on in situ fluorescent derivation of TCs, transferring weakly fluorescing TCs to highly fluorescent species, on alkaline-activated solid silica gel G plates (SGGPs). By coupling solid-surface fluorescence (SSF) with charge-coupled device (CCD) camera imaging, a CCD camera-based SSF (CCD-SSF) methodology has been developed. Calibration curve, repeatability, selectivity, limit of detection (LOD), and limit of quantification (LOQ) have been explored for evaluating the performance of the method itself. Linear calibration curves were obtained over a range of 0.20-1.0 ng/spot for all three TCs. The LODs, defined as 3sigma, for TC, OTC, and CTC were 0.14, 0.15, and 0.16 ng/spot, respectively. The trueness of method was validated by HPLC, and no significant difference between CCD-SSF and HPLC was found, on a basis of 95% confidence level. By spiked recovery studies, a linear calibration curve ranging from 20 to 300 microg/kg of TC in fish muscle samples with a correlation coefficient (R 2) equal to 0.994 was obtained. The total average recovery for TC in fish muscle samples from six different fish matrices, fortified with TC at 50, 100, and 200 microg/kg levels, was 75.7% with average relative standard deviations (RSDs) ranging from 2.0 to 7.7%. RSDs ranged from 2.5 to 5.8% and from 5.2 to 7.6% for in-day and interday repeatability, respectively. The detection and quantification limits in fish muscle matrices were 16 and 53 microg/kg of TCs, respectively. The newly developed CCD-SSF method has been applied to the screening of the TC residues in fish muscle samples. The method has been demonstrated to bear some advantages, such as its simplicity, high throughput, low cost, use of fewer pollutants, and reasonable sensitivity.

[Determination of tetracyclines by a new spectrum technique].

Tetracyclines are light-fluorescence substances, which cannot be detected directly by fluorometry. Herein a new spectrum method was proposed to detect tetracyclines directly by fluorometry. Under optimal conditions, the calibration graph is linear over the range 0.10-9.00 microg x mL(-1) for tetracyclines, and the detection limits of tetracycline, oxytetracycline, chlortetracycline and doxycycline are 0.065, 0.067, 0.068 and 0.070 microg x mL(-2), respectively.

New approach for the detection of peptide- and protein-based radicals using a pre-fluorescent probe.

A novel application for pre-fluorescent probes in the detection of peptide- and protein-based radicals is proposed. Pre-fluorescent probes combine a fluorescent moiety labeled with a paramagnetic nitroxide that acts as a fluorescence quencher. Trapping of a radical by the nitroxide group restores the fluorescence properties. The increase in fluorescence intensity with time reflects the formation and quenching of free radicals and can be employed for the quantitative evaluation of yields and kinetics. In this test system, the pre-fluorescent probe 4-(9-acridinecarbonate)-2,2,6,6-tetramethylpiperidinyl-1-oxyl radical (Ac-Tempo), in which an acridine moiety was labeled with 2,2,6,6-tetramethylpiperidinyl-1-oxy (Tempo), was employed to probe peptide- and protein-based radicals. Peptide-based radicals were generated through the reaction between horseradish peroxidase (HRP)/H(2)O(2) and a derivative of tyrosine. Protein-based radicals were generated through the reaction between myoglobin (Mb) and H(2)O(2). In both cases the Ac-Tempo was found, using a combination of high-performance liquid chromatography (HPLC) and mass spectrometry, to be converted into fluorescent acridine (Ac)-piperidine (4-(9-acridinecarbonate)-2,2,6,6-tetramethylpiperidine).

Probing the hydroxyl radical-mediated reactivity of peroxynitrite by a spin-labeling fluorophore.

The decomposition of peroxynitrite at physiological pH yielded a hydroxyl radical, which reacted rapidly with dimethyl sulfoxide (DMSO) to produce a methyl radical (*CH3), which was then trapped by a spin-label fluorophore nitroxide-linked naphthalene (NTEMPO), a carbon-centered radical probe with a low fluorescence intensity, and transformed to a stable diamagnetic O-alkoxyamine, a high-fluorescence compound. The fluorescence increment was proportional to the concentration of the hydroxyl radical, and then to the concentration of peroxynitrite. NTEMPO therefore was demonstrated to be capable of detecting hydroxyl radicals generated from peroxynitrite, and the method was proved to be simple and sensitive. The hydroxyl radical-mediated reactivities of peroxynitrite to several amino acids, such as tyrosine, phenylalanine and histidine, were then evaluated by the spin-labeling fluorophore NTEMPO at pH 7.4 and, 37 degrees C. The obtained data were in good agreement with the reference values, respectively.

Fluorimetric determination of hemoglobin using spiro form rhodamine B hydrazide in a micellar medium.

A novel fluorimetric method for the determination of hemoglobin (Hb) using spiro form rhodamine B hydrazide (RBH) as fluorogenic reagent in the presence of sodium dodecylbenzene sulfonate (SDBS) surfactant micelles is described. The method employs the reaction of Hb with RBH, a colorless, non-fluorescent spirolactam hydrazide in SDBS micelles to generate highly fluorescent product rhodamine B and hence leads to a large increase in fluorescence intensity. The fluorescence increase is linearly related to the concentration of Hb in the range 0.2-12.0 nmol l(-1) with a detection limit of 0.086 nmol l(-1) (3sigma). The optimal conditions for the detection of Hb are evaluated and the possible detection mechanism is also discussed. The proposed method has been applied to the determination of Hb in human blood.

Development of a novel rhodamine-type fluorescent probe to determine peroxynitrite.

A novel method for the determination of peroxynitrite using rhodamine B hydrazide as a fluorogenic probe is described. The method is based on the oxidation of rhodamine B hydrazide, a colorless, non-fluorescent substance, by peroxynitrite to give rhodamine B-like fluorescence emission. The fluorescence increase is linearly related to the concentration of peroxynitrite in the range of 7.5x10(-8)-3.0x10(-6) mol l(-1) with a detection limit of 2.4x10(-8) mol l(-1) (3sigma). The optimal conditions for the detection of peroxynitrite were evaluated and the possible detection mechanism was also discussed in this paper.