Fluorescent/magnetic nano-aggregation via electrostatic force between modified quantum dot and iron oxide nanoparticles for bimodal imaging of U87MG tumor cells.

Imaging technology based on novel nanomaterials is burgeoning as a potential tool for exploring various physiological processes. We herein report a fluorescent and magnetic nanoprobe (QMNP-RGD) for bimodal imaging of in vitro tumor cells. The preparation of this multifunctional nanomaterial is divided into three steps. First, commercial quantum dots (QDs) with high fluorescence intensity are covalently modified with an RGD peptide, which can facilitate the tumor cell uptake by αvß3 integrin-induced active recognition. Superparamagnetic iron oxide (SPIO) nanoparticles (NPs) are then capped using a cationic polysaccharide to improve stability. Integration is finally achieved by convenient electrostatic binding. We successfully demonstrated that QMNP-RGD can be efficiently delivered into U87MG cells and used for fluorescence/magnetic resonance (MR) bimodal imaging. Other multimodal probes may be able to be designed for imaging based on this strategy of electrostatic binding.

Multifunctional Magnetic CuS/Gd2O3 Nanoparticles for Fluorescence/Magnetic Resonance Bimodal Imaging-Guided Photothermal-Intensified Chemodynamic Synergetic Therapy of Targeted Tumors.

Chemodynamic therapy (CDT), which consumes endogenous hydrogen peroxide (H2O2) to generate reactive oxygen species (ROS) and causes oxidative damage to tumor cells, shows tremendous promise for advanced cancer treatment. However, the rate of ROS generation based on the Fenton reaction is prone to being restricted by inadequate H2O2 and unattainable acidity in the hypoxic tumor microenvironment. We herein report a multifunctional nanoprobe (BCGCR) integrating bimodal imaging and photothermal-enhanced CDT of the targeted tumor, which is produced by covalent conjugation of bovine serum albumin-stabilized CuS/Gd2O3 nanoparticles (NPs) with the Cy5.5 fluorophore and the tumor-targeting ligand RGD. BCGCR exhibits intense near-infrared (NIR) fluorescence and acceptable r1 relaxivity (∼15.3 mM-1 s-1) for both sensitive fluorescence imaging and high-spatial-resolution magnetic resonance imaging of tumors in living mice. Moreover, owing to the strong NIR absorbance from the internal CuS NPs, BCGCR can generate localized heat and displays a high photothermal conversion efficiency (30.3%) under 980 nm laser irradiation, which enables photothermal therapy and further intensifies ROS generation arising from the Cu-induced Fenton-like reaction for enhanced CDT. This synergetic effect shows such an excellent therapeutic efficacy that it can ablate xenografted tumors in vivo. We believe that this strategy will be beneficial to exploring other advanced nanomaterials for the clinical application of multimodal imaging-guided synergetic cancer therapies.

Micro-/nano-fluidic devices and in vivo fluorescence imaging based on quantum dots for cytologic diagnosis.

Semiconductor quantum dots (QDs) possess attractive merits over traditional organic dyes, such as tunable emission, narrow emission spectra and good resistance against optical bleaching, and play a vital role in biosensing and bioimaging for cytologic diagnoses. Microfluidic technology is a potentially useful strategy, as it provides a rapid platform for tracing of disease markers. In vivo fluorescence imaging (FI) based on QDs has become popular for the analysis of complex biological processes. We herein report the applications of multifunctional fluorescent QDs as sensitive probes for diagnoses on cancer medicine and stem cell therapy via microfluidic chips and in vivo imaging.

Fluorescence detections of hydrogen peroxide and glucose with polyethyleneimine-capped silver nanoclusters.

Detection of hydrogen peroxide is of significant importance for biological assays, and fluorescence methods are intensively reported for this purpose. Due to the highly oxidative property of this species, usually fluorescence quenching is obtained during the interactions and decreased signals are rendered. In this report, this oxidative property was adopted for an increased fluorescence signaling. Photoluminescent silver nanoclusters (AgNCs) were synthesized with polyethyleneimine as the stabilizer. This fluorescence from these nanoclusters could be quenched by reduced glutathione (GSH) through an interaction from its thiol group. As an oxidant, hydrogen peroxide converted GSH into an oxidized form (GSSG) with an elimination of the free thiols, and inhibited the quenching. This interaction presented an increased response toward hydrogen peroxide in the range of 0.1-20 µM with a detection limit of 35 nM. The scheme was further coupled with glucose oxidase for a glucose analysis down to 0.11 µM. This method was selective and was successfully applied for glucose measurement in human serum samples.

Fluorometric determination of nitrite through its catalytic effect on the oxidation of iodide and subsequent etching of gold nanoclusters by free iodine.

A method for sensitive detection of nitrite is presented. It is found that the red fluorescence of gold nanoclusters (with excitation/emission maxima at 365/635 nm) is quenched by traces of iodine via etching. Free iodide is formed by oxidation of iodide by bromate anion under the catalytic effect of nitrite. This catalytic process provides a sensitive means for nitrite detection. Under the optimal conditions, fluorescence linearly dropos in the 10 nM to 0.8 µM nitrite concentration range. The limit of detection is 1.1 nM. This is a few orders of magnitude lower than the maximum concentration allowed by authorities. Graphical abstract Schematic representation of a method for detection of nitrite via a redox reaction. Iodine was produced in the reaction and subsequently quenched the fluorescence from gold nanoclusters by etching their metallic cores, and a sensitive assay for nitrite down to 1.1 nM was developed.

Determination of alkaline phosphatase activity based on enzyme-triggered generation of a thiol and the fluorescence quenching of silver nanoclusters.

A fluorimetric method is described for the determination of alkaline phosphatase (ALP) activity. It is based on the use of polyethyleneimine-coated silver nanoclusters (AgNCs), which display an intense blue fluorescence peaking at 450 nm (under 375 nm excitation). ALP catalyzes the dephosphorylation of the thiophosphate amifostine to generate a thiol that binds to the AgNCs and causes its fluorescence to be quenched. Under the optimal experimental conditions, fluorescence linearly drops in the 0.08-2.0 U L-1 ALP activity range, and the limit of detection is 0.02 U L-1. The method was successfully applied to the determination of ALP activity in spiked human serum samples. Graphical abstract Alkaline phosphatase (ALP) catalyzes the degradation of amifostine with a generation a thiol product. The thiol quenches the fluorescence of silver nanoclusters, and a method for the detection of ALP down to 0.02 U L-1 was developed.

Copper ion detection with improved sensitivity through catalytic quenching of gold nanocluster fluorescence.

In this report, a sensitive fluorescence detection of copper (Ⅱ) ion was developed. Although itself only a weak quencher toward gold nanocluster fluorescence, this ion functioned as a catalyst that accelerated the oxidation of iodide into iodine by a strong oxidant. The so-produced iodine quenched the nanocluster fluorescence through an efficient etching reaction, which rendered a much improved sensitivity for copper detection. Under the optimal conditions, the extent of quenching was found linear to the amount of copper in the range of 0.8-80 nM, and this strategy was capable of detecting copper ion as low as 0.33 nM. The method was selective and was successfully applied for related measurement in practical samples.

Gold nanocluster-based ratiometric fluorescent probes for hydrogen peroxide and enzymatic sensing of uric acid.

A method is described for ratiometric fluorometric assays of H2O2 by using two probes that have distinct response profiles. Under the catalytic action of ferrous ion, the 615 nm emission of protein-stabilized gold nanoclusters (under 365 nm photoexcitation) is quenched by H2O2, while an increased signal is generated with a peak at 450 nm by oxidizing coumarin with the H2O2/Fe(II) system to form a blue emitting fluorophore. These decrease/increase responses give a ratiometric signal. The ratio of the fluorescences at the two peaks are linearly related to the concentration of H2O2 in the range from 0.05 to 10 µM, with a 7.7 nM limit of detection. The detection scheme was further coupled to the urate oxidase catalyzed oxidation of uric acid which proceeds under the formation of H2O2. This method provides an simple and effective means for the construction of ratiometric fluorometric (enzymatic) assays that involve the detection of H2O2. Graphical abstract Under catalysis by ferrous ion, hydrogen peroxide quenches the luminescence of gold nanoclusters (AuNCs) and oxidizes coumarin into a fluorescent derivative, which rendered fluorescence ON and OFF at two distinct wavelengths for ratiometric measurements.