A Dual-Functional Ferroferric Oxide/Quantum Dots Theranostic Nanoplatform for Fluorescent Labeling and Photothermal Therapy

A biocompatible, nontoxic theranostic nanoplatform consisting of mesoporous silica-coated ferroferric oxide (Fe₃O₄) and Mn-doped ZnS-ZnS quantum dots (QDs) is synthesized via a layer-by-layer method. Transmission electron microscopy, X-ray diffractometer, magnetometry, and fluorophotometer are employed to characterize the nanoplatform. The nanoplatform exhibits excellent superparamagnetic, fluorescent, and light absorption properties. The template method is introduced to form a mesoporous silica structure on the nanoplatform, lowering the mass of the nanoplatform and effectively promoting the absorption efficiency of the incident light compared with the traditional silica layer. In addition, after endocytosis of the nanoplatform, cancer cells are easily detected under a fluorescence microscope because of the excellent fluorescent behavior of QDs. Moreover, in vitro experiments confirm that nanoplatform possesses perfect photothermal effect to destroy tumor cells under laser irradiation. Therefore, ferroferric oxide/QDs nanoplatforms, combined with the functions of fluorescent labeling and photothermal therapy for cancer cells, are expected to be a promising biopotential material in the field of diagnosis and treatment.     

Fluorescence correlation spectroscopy of CdSe/ZnS quantum dot optical bioimaging probes with ultra-thin biocompatible coatings

The colloidal stabilities and emission properties of CdSe/ZnS quantum dot (QD) optical probes capped with a variety of thin, hydrophilic surface coatings were studied using confocal fluorescence correlation spectroscopy. These coatings are based on mercaptoethanol, mercaptopropionic acid (with and without conjugated aminoethoxyethanol), lipopolymers (DSPE-PEG2000), cysteine (Cys), and a variety of Xaa-Cys dipeptides. The study shows that QDs with thin hydrophilic coatings can be designed that combine good colloidal stability and excellent emission properties (brightness). Furthermore, there is a general correlation between colloidal stability and brightness. The experiments reported illustrate that QDs with multiple types of thin coatings can be created for optical imaging applications in a biological environment while also maintaining a size below 10 nm.     

Facile synthesis of mercaptosuccinic acid-capped CdTe/CdS/ZnS core/double shell quantum dots with improved cell viability on different cancer cells and normal cells

Water-soluble, mercaptosuccinic acid (MSA)-capped CdTe/CdS/ZnS core/double shell quantum dots (QDs) were prepared by successive growth of CdS and ZnS shells on the as-synthesized CdTe/CdS_thin core/shell quantum dots. The formation of core/double shell structured QDs was investigated by ultraviolet-visible (UV–Vis) absorption and photoluminescence (PL) spectroscopy, PL decay studies, X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). The core/double shell QDs exhibited good photoluminescence quantum yield (PLQY) which is 70% higher than that of the parent core/shell QDs, and they are stable for months. The average particle size of the core/double shell QDs was ～3 nm as calculated from the transmission electron microscope (TEM) images. The cytotoxicity of the QDs was evaluated on a variety of cancer cells such as HeLa, MCF-7, A549, and normal Vero cells by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) cell viability assay. The results showed that core/double shell QDs were less toxic to the cells when compared to the parent core/shell QDs. MCF-7 cells showed proliferation on incubation with QDs, and this is attributed to the metalloestrogenic activity of cadmium ions released from QDs. The core/double shell CdTe/CdS/ZnS (CSS) QDs were conjugated with transferrin and successfully employed for the biolabeling and fluorescent imaging of HeLa cells. These core/double shell QDs are highly promising fluorescent probe for cancer cell labeling and imaging applications.     

Cytotoxicity and fluorescence studies of silica-coated CdSe quantum dots for bioimaging applications

The toxicological effects of silica-coated CdSe quantum dots (QDs) were investigated systematically on human cervical cancer cell line. Trioctylphosphine oxide capped CdSe QDs were synthesized and rendered water soluble by overcoating with silica, using aminopropyl silane as silica precursor. The cytotoxicity studies were conducted by exposing cells to freshly synthesized QDs as a function of time (0–72 h) and concentration up to micromolar level by Lactate dehydrogenase assay, MTT [3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide] assay, Neutral red cell viability assay, Trypan blue dye exclusion method and morphological examination of cells using phase contrast microscope. The in vitro analysis results showed that the silica-coated CdSe QDs were nontoxic even at higher loadings. Subsequently the in vivo fluorescence was also demonstrated by intravenous administration of the QDs in Swiss albino mice. The fluorescence images in the cryosections of tissues depicted strong luminescence property of silica-coated QDs under biological conditions. These results confirmed the role of these luminescent materials in biological labeling and imaging applications.     

Fluorescence Analysis with Quantum Dot Probes for Hepatoma Under One- and Two-Photon Excitation

A new class of fluorescent probe produced by conjugating semiconductor quantum dots (QDs) with protein molecule is proposed as an alternative to conventional organic labels. However the fluorescence characteristics of the QD bioconjugates are not clear while they are excitied with one- or two-photon laser pulse. We synthesized specific immunofluorescent probes by linking QDs to alpha fetoprotein (AFP) antibody for specific binding alpha-fetoprotein -an important marker for hepatocellular carcinoma cell lines, and archived specific fluorescence detection with the QDs-Anti-AFP in nude mice. Then, we have analyzed the fluorescence characteristics of QDs-Anti-AFP and original QDs both under one- and two-photon excitations. The results demonstrated that QDs-Anti-AFP's fluorescent spectral and lifetime haven't varied much from that of original QDs. Moreover, QDs-Anti-AFP have exhibited higher fluorescence efficiency than QDs under two-photon examination.     

水热法快速制备荧光氧化石墨烯量子点及其在细胞成像中的应用

作为一种新型荧光纳米材料,氧化石墨烯量子点(GO QDs)凭借其良好的水溶性和生物相容性得到广泛的关注。以氧化石墨烯为原料,过氧化氢为氧化剂,一步水热法在90 min内快速制备氧化石墨烯量子点,实现了快速、高效及绿色制备氧化石墨烯量子点。所制备得到的氧化石墨烯量子点分布均匀,透射电镜(TEM)图片表明氧化石墨烯量子点粒径分布在2.25～5.25 nm,傅里叶红外光谱(FTIR)和X射线电子能谱(XPS)显示氧化石墨烯量子点表面含有大量的羟基、羧基、羰基等含氧功能团,表明氧化石墨烯量子点具有很好的水溶性。荧光发射光谱(PL)表明氧化石墨烯量子点具有激发波长依赖性。基于其独特的纳米结构,良好的光学性能和生物相容性,氧化石墨烯量子点可替代传统荧光纳米材料应用于细胞成像。     

平均探测时间:研究单个量子点荧光现象的另一种思路

Due to photoluminescence intermittency of single colloidal quantum dots (QDs), the traditional exponential fluorescence lifetime analysis is not perfect to characterize QDs'' fluorescent emission behavior. In this work we used the time-tagged time-resolved (TTTR) mode to record the fluorescent photons from single QDs. We showed that this method is compatible with the traditional lifetime analysis. In addition, by constructing the trajectory over time and the distribution of average arrival time (AAT) of the fluorescent photons, more details about the emission behavior of QDs were revealed.     

A feasible method of improving the quantum yield of CdTe/CdS quantum dots by the first heating–cooling cycle and their application in cancer cell recognition

In this article, water-soluble CdTe/CdS quantum dots (QDs) were synthesized in aqueous solution with captosuccinic acid as stabilizer. The absorption and fluorescence spectra showed that the as-prepared QDs had good optical properties. It was observed that the quantum yield (QY) of QDs was greatly increased after a heating–cooling cycle (from 22 to 41%). Then, the QDs were used to prepare fluorescent probes. The experiment results showed that the transferrin (Tf) could conjugate to QDs effectively and the HepG2 cells could be recognized successfully. This study is of great significance for the preparation of high-quality QDs and their applications in life science.     

CdTe QDs-based prostate-specific antigen probe for human prostate cancer cell imaging

l-glutathione (GSH) stabilized CdTe quantum dots (QDs) were directly prepared in aqueous solution. The as-prepared QDs were linked to prostate-specific antigen (PSA) for the direct labeling and linked to immunoglobulin G (IgG) for the indirect labeling of fixed prostate cancer cells. The results indicated that QD-based probes were ideal fluorescent markers with excellent spectral properties and photostability and much better than organic dyes making them very suitable in target detection. Meanwhile, the indirect labeling showed much better specificity than the direct labeling. Furthermore, the prepared CdTe QDs did not show detectable effect on cell growth after having cultured for three days, which suggested that the l-glutathione capped CdTe had scarcely cytotoxicity.     

Determining the effective density of airborne nanoparticles using multiple charging correction in a tandem DMA/ELPI setup

The cysteamine-modified hyaluronic acid (HA) polymer was employed to coat quantum dots (QDs) through a convenient one-step reverse micelle method, with the final QDs hydrodynamic size of around 22.6 nm. The HA coating renders the QDs with very good stability in PBS for more than 140 days and resistant to large pH range of 2–12. Besides, the HA-coated QDs also show excellent fluorescence stability in BSA-containing cell culture medium. In addition, the cell culture assay indicates no significant cytotoxicity for MD-MB-231 breast cancer cells, and its targeting ability to cancer receptor CD44 has been demonstrated on two breast cancer cell lines. The targeting mechanism was further proved by the HA competition experiment. This work has established a new approach to help solve the stability and toxicity problems of QDs, and moreover render the QDs cancer targeting property. The current results indicate that the HA polymer-coated QDs hold the potential application for both in vitro and in vivo cancer imaging researches.     

Self-assembly of dandelion-like Fe3O4@C@BiOCl magnetic nanocomposites with excellent solar-driven photocatalytic properties

In comparison with conventional organic dyes, quantum dots (QDs) have unique optical and electronic properties, which provide QDs with a wide scope of prospective application in biology and biomedicine. However, the toxicity of QDs and the fluorescence intensity of labeled bacteria must precede their application in bacterial imaging and tracing in vivo. Here, we show that treatment with CaCl₂ significantly improved bacterial labeling efficiency of CdSe/ZnS QDs with the CdSe core size of ~3.1 nm (relative fluorescence unit (RFU) value and ratio of fluorescent E. coli) with rising CdSe/ZnS QDs concentration in a concentration-dependent manner. At 12.5 nmol/L CdSe/ZnS QDs concentration, labeled Escherichia coli (E. coli) DH5α appeared as short rod-shaped and luminescent with normal size, and the survival rate and ultrastructure did not change in comparison to the control. But the ratio of fluorescent bacteria and RFU were very low. However, the survival rate of transformed E. coli was significantly inhibited by high CdSe/ZnS QDs concentrations (≥25 nmol/L). Moreover, internalization of CdSe/ZnS QDs resulted in ultrastructure damage of transformed E. coli in a concentration-dependent manner (≥25 nmol/L). Therefore, CdSe/ZnS QDs may not suitable for tracing of bacteria in vivo. Moreover, our study also revealed that colony-forming capability assay and transmission electron microscopy could be used to comprehensively evaluate the toxicity of QDs on labeled bacteria. Our findings do provide a new direction toward the improvement and modification of QDs for use in imaging and tracing studies in vivo.     

A Novel Homogeneous Time-Resolved Fluoroimmunoassay for Carcinoembryonic Antigen Based on Water-Soluble Quantum Dots

Quantum dots are not widely used in clinical diagnosis. However, the homogeneous time-resolved fluorescence assay possesses many advantages over current methods for the detection of carcinoembryonic antigen (CEA), a primary marker for many cancers and diseases. Therefore, a novel luminescent terbium chelates- (LTCs) and quantum dots-based homogeneous time-resolved fluorescence assay was developed to detect CEA. Glutathione-capped quantum dots (QDs) were prepared from oil-soluble QDs with a 565 nm emission peak. Conjugates (QDs-6 F11) were prepared with QDs and anti-CEA monoclonal antibody. LTCs were prepared and conjugates (LTCs-S001) were prepared with another anti-CEA monoclonal antibody. The fluorescence lifetime of QDs was optimized for sequential analysis. The Förster distance (R₀) was calculated as 61.9 Å based on the overlap of the spectra of QDs-6 F11 and LTCs-S001. Using a double-antibody sandwich approach, the above antibody conjugates were used as energy acceptor and donor, respectively. The signals from QDs were collected in time-resolved mode and analyzed for the detection of CEA. The results show that the QDs were suitable for time-resolved fluoroassays. The spatial distance of the donor-acceptor pair was calculated to be 61.9 Å. The signals from QDs were proportional to CEA concentration. The standard curve was LogY?=?2.75566?+?0.94457 LogX (R?=?0.998) using the fluorescence counts (Y) of QDs and the concentrations of CEA (X). The calculated sensitivity was 0.4 ng/mL. The results indicate that water-soluble QDs are suitable for the homogenous immunoassay. This work has expanded future applications of QDs in homogeneous clinical bioassays. Furthermore, a QDs-based homogeneous multiplex immunoassay will be investigated as a biomarker for infectious diseases in future research.     

Non-specific interactions of CdTe/Cds Quantum Dots with human blood mononuclear cells

In order to study biological events, researchers commonly use methods based on fluorescence. These techniques generally use fluorescent probes, commonly small organic molecules or fluorescent proteins. However, these probes still present some drawbacks, limiting the detection. Semiconductor nanocrystals - Quantum Dots (QDs) - have emerged as an alternative tool to conventional fluorescent dyes in biological detection due to its topping properties - wide absorption cross section, brightness and high photostability. Some questions have emerged about the use of QDs for biological applications. Here, we use optical tools to study non-specific interactions between aqueous synthesized QDs and peripheral blood mononuclear cells. By fluorescence microscopy we observed that bare QDs can label cell membrane in live cells and also label intracellular compartments in artificially permeabilized cells, indicating that non-specific labeling of sub-structures inside the cells must be considered when investigating an internal target by specific conjugation. Since fluorescence microscopy and flow cytometry are complementary techniques (fluorescence microscopy provides a morphological image of a few samples and flow cytometry is a powerful technique to quantify biological events in a large number of cells), in this work we also used flow cytometry to investigate non-specific labeling. Moreover, by using optical tweezers, we observed that, after QDs incubation, zeta potentials in live cells changed to a less negative value, which may indicate that oxidative adverse effects were caused by QDs to the cells.     

Silica-coated quantum dots fluorescent spheres synthesized using a quaternary ‘water-in-oil’ microemulsion system

Nanoscale and microscale silica spheres embedded with multiple CdSe quantum dots (QDs, having average diameters of about 2.4 and 5.0 nm, respectively.) were synthesized by using a quaternary ‘water-in-oil’ microemulsion. Comparing the uncoated QDs, the quantum yields (QYs) of the silica-coated QD spheres were enhanced when the QD cores were synthesized using mercaptoacetic acid (MA) as a stabilizer, while the QYs were dramatically decreased when the cores were synthesized using citric acid (CA) as a stabilizer. The enhanced QYs could be further improved by heating the silica-coated QDs in aqueous solution. Although the QYs of the silica-coated QDs were not high, these spheres emitted bright fluorescence. The silica shells contained numerous micropores (∼0.58–0.91 nm), and small amounts of toxic ions (such as Cd²⁺) could be released from the silica spheres. However, the release rate of toxic ions from the silica spheres was significantly reduced compared with that of the uncoated QDs.     

Fluorescence Imaging of Stem Cells,Cancer Cells and Semi-Thin Sections of Tissues using Silica-Coated CdSe Quantum Dots

Trioctylphosphine oxide capped cadmium selenide quantum dots, synthesized in organic media were rendered water soluble by silica overcoating. Silanisation was done by a simple reverse microemulsion method using aminopropyl silane as the silica precursor. Further, the strong photoluminescence of the silica-coated CdSe quantum dots has been utilized to visualize rabbit adipose tissue-derived mesenchymal stem cells (RADMSCs) and Daltons lymphoma ascites (DLA) cancerous cells in vitro. Subsequently the in vivo fluorescence behaviours of QDs in the tissues were also demonstrated by intravenous administration of the QDs in Swiss albino mice. The fluorescence microscopic images in the stem cells, cancer cells and semi-thin sections of mice organs proved the strong luminescence property of silica-coated quantum dots under biological systems. These results establish silica-coated CdSe QDs as extremely useful tools for molecular imaging and cell tracking to study the cell division and metastasis of cancer and other diseases.     

Photoluminescence quenching of CdTe/CdS core-shell quantum dots in aqueous solution by ZnO nanocrystals

Photoluminescence (PL) properties of 3-mercaptopropionic acid (MPA) coated CdTe/CdS core-shell quantum dots (QDs) in aqueous solution in the presence of ZnO colloidal nanocrystals were studied by steady-state and time-resolved PL spectroscopy. The PL quenching of CdTe/CdS core-shell QDs with addition of purified ZnO nanocrystals resulted in a decrease in PL lifetime and a small red shift of the PL band. It was found that CdTe(1.5 nm)/CdS type II core-shell QDs exhibited higher efficiency of PL quenching than the CdTe(3.0 nm)/CdS type I core-shell QDs, indicating an electron transfer process from CdTe/CdS core-shell QDs to ZnO nanocrystals. The experimental results indicated that the efficient electron transfer process from CdTe/CdS core-shell QDs to ZnO nanocrystals could be controlled by changing the CdTe core size on the basis of the quantum confinement effect.     

Plasma kinetics and biodistribution of water-soluble CdTe quantum dots in mice: a comparison between Cd and Te

Water-soluble quantum dots (QDs) have shown potential as tumor diagnostic agents. However, little is known about their biological behaviors in vivo. Male ICR mice were intravenously given a single dose (2.5 ??mol kg^?1 body weight) of water-soluble cadmium?Ctelluride (CdTe) QDs (the QDs are approximately 4 nm in diameter and have maximal emission at 630 nm). Inductively coupled plasma mass spectrometry (ICP-MS) was used for measuring the kinetic action of ¹¹¹Cd and ¹²⁵Te for 7 days. The plasma kinetics of Cd and Te followed a two-compartment model, in which Cd exhibited greater apparent volume of distribution, greater clearance, faster distribution half-life, and significantly slower elimination half-life compared to Te. Contrary to its relatively transient fate in the plasma, high levels of Cd persisted in the liver and kidneys. Te accumulated primarily in the spleen. The different plasma kinetics and distribution patterns of Cd and Te imply that CdTe QDs have been part of the degradation or aggregation in vivo.     

Spectroscopic study of oscillator strength and radiative decay time of colloidal CdSe quantum dots

Characterization of samples of cadmium selenide quantum dots (CdSe) QDs dissolved in toluene colloidal solutions at a concentration of 1.4 mg/ml was carried out through UV–Vis absorption and photoluminescence (PL) spectroscopy. The size-dependent absorption and red-shifted PL emission peak wavelengths could be tuned between 510–576 and 545–606 nm respectively. Optical absorption spectral measurements yielded CdSe QDs having diameters about ~ 2.44–3.69 nm with energy gaps 2.32–2.08 eV which are higher than the bulk CdSe (1.74 eV) reminiscent of quantum confinement. This is found to be in good agreement with the semi-empirical pseudopotential model. In addition, the first excitonic absorption transition 1S_(e)1S_3/2(h) oscillator strength and the corresponding fluorescence radiative decay time of CdSe QDs are assessed using relevant Einstein relations for absorption and emission in a two-level system. The elaborated calculations would anticipate that the transition oscillator scale with the CdSe QD radius as ~ R^2.54. Correspondingly, the calculated radiative decay times decrease from 56.4 to 23.2 ns which scale with CdSe QDs radius as ~ R^?2.155 in fairly good agreement with experimental values reported in the literature.     

RGDS-conjugated CdSeTe/CdS quantum dots as near-infrared fluorescent probe: preparation,characterization and bioapplication

In the experiments, high-quality, water-soluble and near-infrared (NIR)-emitting CdSeTe and CdSeTe/CdS quantum dots (QDs) were successfully prepared. The average size of CdSeTe?CdS QDs was 7.68 nm and CdSeTe QDs was 4.33 nm. Arginine-glycine-aspartic-serine acid (RGDS) peptides were linked to CdSeTe/CdS QDs by N-(3-(dimethylamino)propyl)-N′-ehtylcarbodiimide hydrochloride (EDC) and N′-hydroxysuccinimide (NHS). The prepared RGDS-tagged NIR CdSeTe/CdS QDs (denoted as RGDS-CdSeTe/CdS) had an average diameter of 24.83 nm and were used for cancer cell immunofluorescence imaging. The characteristics of RGDS-conjugated CdSeTe/CdS such as morphology, structure, spectra, stability, cytotoxicity, and near-infrared microscopic imaging were investigated in detail. HepG2 cells were incubated with the novel fluorescent probe (RGDS-CdSeTe/CdS), which realized immunofluorescence targeting and imaging. The results reported here open up new perspectives for integrin-targeted near-infrared imaging and may aid in tumor detection including imaging-guided surgery.     

Microwave-Assisted Aqueous Synthesis of Highly Luminescent Carboxymethyl Chitosan-Coated CdTe/CdS Quantum Dots as Fluorescent Probe for Live Cell Imaging

This paper describes the development of a simplified and rapid method for the aqueous synthesis of quantum dots (QDs) with CdTe cores and gradient CdS external shells (CdTe/CdS QDs) aided by microwave irradiation. Several synthesis parameters, such as molar ratio of reagents, pH, reaction temperature, and reaction time, were studied in details. Under the optimized conditions, highly effective CdTe/CdS QDs could be synthesized in aqueous phase in only 15 min. In order to improve the biocompatibility of the CdTe/CdS QDs, these QDs were then interacted with carboxymethyl chitosan (CMC) so as they could be used as fluorescent probes in the aqueous phase. With the incorporation of CMC, the stability of modified QDs was found to have improved significantly (from 4 months to more than 10 months at room temperature). The photoluminescence quantum yield (PLQY) of the modified QDs could reach 75%, other parameters include a full width at half maximum of the emission (FWHM) spectrum as 40 ~ 60 nm, and an average size, estimated from electron microscopic images, as 3.5 nm. As fluorescent probes, these modified QDs were successfully used for imaging live Madin–Darby canine kidney (MDCK) cells, in which the preliminary results indicated that these modified QDs demonstrated good biocompatibility and showed promising applications for bio-labeling and imaging.