Folate Conjugated CdHgTe Quantum Dots with High Targeting Affinity and Sensitivity for In vivo Early Tumor Diagnosis

CdHgTe-folate conjugates, acting as novel active-targeting fluorescence probes, were prepared by covalent conjugation of CdHgTe QDs and folic acid. Their characteristics, such as optical spectra, stability and cancer cell targeting were investigated in detail. The fluorescence wavelength of CdHgTe-folate conjugates was 790 nm and a full width at half-maximum (FWHM) of them was 50–70 nm. Their fluorescence stability could satisfy the need of long and continuous fluorescence imaging. The in vivo dynamic bio-distribution of CdHgTe-folate conjugates in S180 tumor beard mouse model was monitored by a NIR imaging system. The resultes indicated that CdHgTe-folate conjugates targeted to tumor effectively. The high fluorescence intensity together with targeting effect makes CdHgTe-folate conjugates promising candidates for imaging, monitoring and early diagnosis of cancer at molecular and cell level.     

Synthesis of AS1411-Aptamer-Conjugated CdTe Quantum Dots with High Fluorescence Strength for Probe Labeling Tumor Cells

In this paper, we report microwave-assisted, one-stage synthesis of high-quality functionalized water-soluble cadmium telluride (CdTe) quantum dots (QDs). By selecting sodium tellurite as the Te source, cadmium chloride as the Cd source, mercaptosuccinic acid (MSA) as the capping agent, and a borate-acetic acid buffer solution with a pH range of 5–8, CdTe nanocrystals with four colors (blue to orange) were conveniently prepared at 100 °C under microwave irradiation in less than one hour (reaction time: 10–60 min). The influence of parameters such as the pH, Cd:Te molar ratio, and reaction time on the emission range and quantum yield percentage (QY%) was investigated. The structures and compositions of the prepared CdTe QDs were characterized by transmission electron microscopy, energy-dispersive X-ray spectroscopy, selective area electron diffraction, and X-ray powder diffraction experiments. The formation mechanism of the QDs is discussed in this paper. Furthermore, AS1141-aptamer-conjugated CdTe QDs in the U87MG glioblastoma cell line were assessed with a fluorescence microscope. The obtained results showed that the best conditions for obtaining a high QY of approximately 87 % are a pH of 6, a Cd:Te molar ratio of 5:1, and a 30-min reaction time at 100 °C under microwave irradiation. The results showed that AS1141-aptamer-conjugated CdTe QDs could enter tumor cells efficiently. It could be concluded that a facile high-fluorescence-strength QD conjugated with a DNA aptamer, AS1411, which can recognize the extracellular matrix protein nucleolin, can specifically target U87MG human glioblastoma cells. The qualified AS1411-aptamer-conjugated QDs prepared in this study showed excellent capabilities as nanoprobes for cancer targeting and molecular imaging.     

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.     

Preparation of Highly Biocompatible ZnSe Quantum Dots Using a New Source of Acetyl Cysteine as Capping Agent

In this paper, we describe a facile method for preparation of ZnSe quantum dots (QDs) using an inexpensive and biocompatible source of acetyl cysteine in aqueous media. The structural properties of the ZnSe QDs have been characterized using XRD, FT-IR, and TEM techniques. The optical properties of the as-prepared QDs were found to be size-dependent, due to the strong confinement regime at relatively low refluxing time. Effect of solution pH and refluxing temperature on absorption and emission characteristics of the ZnSe QDs was studied. The empirical effective mass approximation also reveals that, both solution pH and refluxing temperature parameters would effect on ZnSe QDs growth, and increase their size. However, the influence of the solution pH was found to be more prominent. Water-solubility, high emission intensity and sub-10 nm nanocrystals size are the most essential features that suggest our synthesized aqueous-based ZnSe QDs (with a very cost-effective and biocompatible capping agent) can be utilized for biological intentions.     

Liposome Encapsulation of Thiol-Capped CdTe Quantum Dots for Enhancing the Intracellular Delivery

Although water soluble thiol-capped quantum dots (QDs) have been widely used as photoluminescence (PL) probes in various applications, the negative charges on thiol terminals limit the cell uptake hindering their applications in cell imaging. The commercial liposome complex (Sofast®) was used to encapsulate these QDs forming the liposome vesicles with the loading efficiency as high as about 95%. The cell uptakes of unencapsulated QDs and QD loaded liposome vesicles were comparatively studied by a laser scanning confocal microscope. We found that QD loaded liposome vesicles can effectively enhance the intracellular delivery of QDs in three cell lines (human osteosarcoma cell line (U2OS); human cervical carcinoma cell line (Hela); human embryonic kidney cell line (293 T)). The photobleaching of encapsulated QDs in cells was also reduced comparing with that of unencapsulated QDs, measured by the PL decay of cellular QDs with a continuous laser irradiation in the microscope. The flow cytometric measurements further showed that the enhancing ratios of encapsulated QDs on cell uptake are about 4–8 times in 293 T and Hela cells. These results suggest that the cationic liposome encapsulation is an effective modality to enhance the intracellular delivery of thiol-capped QDs.     

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.     

Manganese Doped Zinc Sulfide Quantum Dots for Detection of Escherichia coli

A novel biocompatible chitosan passivated manganese doped zinc sulfide (Mn doped ZnS) nanophosphor has been synthesized through a simple aqueous precipitation reaction. Upon excitation with ultraviolet light, the quantum dots (QDs) emit an orange luminescence peaking at 590 nm, which is visible to the naked eye. These chitosan coated Mn doped ZnS QDs can have potential applications in bio-labeling, particularly in fluorescence-based imaging. One of the envisioned applications of these QDs is in improving the conventional, organic dye-reliant Fluorescence in situ Hybridization (FISH) technique, a widely used method for microbial detection. Here we demonstrate that the chitosan-capped Mn doped ZnS QDs are suitable for this purpose.     

Emerging spectroscopic techniques for prostate cancer diagnosis

ABSTRACT

Over the past several decades, large efforts have been made to diagnose and overcome prostate cancer. Among all screening methods, the measurement of prostate-specific antigen (PSA) threshold has been stood out and contributed to diagnose prostate cancer (PCa) in a large number of men. Nevertheless, the early detection of prostate carcinoma and its focal imaging is remaining crucial to diminish the elevated number of PCa-related deaths. Because of the multifocal behavior of PCa development, a whole gland ablation has been practiced during previous years. Furthermore, there is an evidence of the likelihood of high-risk PCa that proves once again the importance of early diagnosis and accurate staging of the disease. So far, numerous advanced spectroscopic methods with different approaches have been reported as the alternative tools to conventional techniques of PCa diagnosis and imaging. In this review, we introduce innovative emerging techniques utilizing spectroscopic methods such as photoluminescence, surface-enhanced Raman spectroscopy, and surface plasmon resonance to measure the ultralow level of PSA. In addition, we review novel and alternative approaches of diagnosis such as imaging methods through photoluminescence, magnetic resonance imaging, and positron emission tomography.     

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.     

In Vivo Targeted Cancer Theranostics by Core/Shell‐Structured Multifunctional Prussian Blue/PLGA “Nanococktails”

The construction of high‐performance nanotheranostic agent with Food and Drug Administration (FDA)‐approved materials for efficient treatment of breast cancer is still of great challenge. This work reports, for the first time, on the elaborate integration of two FDA‐approved materials together to construct a multifunctional core/shell‐structured “nanococktail” for cancer theranostics. The biocompatible Prussian blue nanoparticles with high photothermal‐conversion performance are coated by poly(lactic‐co‐glycolic acid) followed by further surface targeting engineering (folic acid conjugation). The anticancer drug paclitaxel is concurrently encapsulated into the nanocarrier with high efficiency and capacity. Especially, these “nanococktails” act as the desirable contrast agents for photoacoustic/magnetic resonance imaging dual‐mode diagnostic imaging, providing the potential for guidance and monitoring during the therapeutic process, which has been systematically demonstrated both in vitro and in vivo. Importantly, these “nanococktails” have demonstrated their high performance in synergistic in vivo photothermal therapy and chemotherapy against breast cancer tumor xenograft. This work not only provides a high‐performance theranostic “nanococktail” platform for efficient theranostic treatment of cancer but also paves a new way for the integration of various functional moieties together for realizing the specific diagnostic imaging‐guided and synergistic cancer therapy.     

Enhancing early bladder cancer detection with fluorescence-guided endoscopic optical coherence tomography

We report an experimental study of the possibility of enhancing early bladder cancer diagnosis with fluorescence-image-guided endoscopic optical coherence tomography (OCT). After the intravesical instillation of a 10% solution of 5-aminolevulinic acid, simultaneous fluorescence imaging (excitation of 380-420 nm, emission of 620-700 nm) and OCT are performed on rat bladders to identify the photochemical and morphological changes associated with uroepithelial tumorigenesis. The preliminary results of our ex vivo study reveal that both fluorescence and OCT can identify early uroepithelial cancers, and OCT can detect precancerous lesions (e.g., hyperplasia) that fluorescence may miss. This suggests that a cystoscope combining 5-aminolevulinic acid fluorescence and OCT imaging has the potential to enhance the efficiency and sensitivity of early bladder cancer diagnosis.     

Modeling of various contact theories for the manipulation of different biological micro/nanoparticles based on AFM

Single-walled carbon nanohorns (SWNHs) have great potential to enhance thermal and chemotherapeutic drug efficiencies for cancer therapies. Despite their diverse capabilities, minimal research has been conducted so far to study nanoparticle intracellular transport, which is an important step in designing efficient therapies. SWNHs, like many other carbon nanomaterials, do not have inherent fluorescence properties making intracellular transport information difficult to obtain. The goals of this project were to (1) develop a simple reaction scheme to decorate the exohedral surface of SWNHs with fluorescent quantum dots (QDs) and improve conjugate stability, and (2) evaluate SWNH–QD conjugate cellular uptake kinetics and localization in various cancer cell lines of differing origins and morphologies. In this study, SWNHs were conjugated to CdSe/ZnS core/shell QDs using a unique approach to carbodiimide chemistry. Transmission electron microscopy and electron dispersive spectroscopy verified the conjugation of SWNHs and QDs. Cellular uptake kinetics and efficiency were characterized in three malignant cell lines: U-87 MG (glioblastoma), MDA-MB-231 (breast cancer), and AY-27 (bladder transitional cell carcinoma) using flow cytometry. Cellular distribution was verified by confocal microscopy, and cytotoxicity was also evaluated using an alamarBlue assay. Results indicate that cellular uptake kinetics and efficiency are highly dependent on cell type, highlighting the significance of studying nanoparticle transport at the cellular level. Nanoparticle intracellular transport investigations may provide information to optimize treatment parameters (e.g., SWNH concentration, treatment time, etc.) depending on tumor etiology.     

Superparamagnetic nanoparticles for biomedical applications: Possibilities and limitations of a new drug delivery system

Nanoparticles can be used in biomedical applications, where they facilitate laboratory diagnostics, or in medical drug targeting. They are used for in vivo applications such as contrast agent for magnetic resonance imaging (MRI), for tumor therapy or cardiovascular disease. Very promising nanoparticles for these applications are superparamagnetic nanoparticles based on a core consisting of iron oxides (SPION) that can be targeted through external magnets. SPION are coated with biocompatible materials and can be functionalized with drugs, proteins or plasmids. In this review, the characteristics and applications of SPION in the biomedical sector are introduced and discussed.     

Enhancement of Intracellular Delivery of CdTe Quantum Dots (QDs) to Living Cells by Tat Conjugation

Quantum dots (QDs), as novel fluorescence probes, have shown a great potential for bio-molecular labeling and cellular imaging. To stain cellular targets, the sufficient intracellular delivery of QDs is required. In this work the tat, a typical membrane-permeable carrier peptide, was conjugated with thiol-capped CdTe QDs to form CdTe Tat-QDs, and the intracellular deliveries of CdTe QDs or CdTe Tat-QDs were compared in human hepatocellular carcinoma (QGY) cells and human breast cancer (MCF7) cells in vitro by means of confocal laser scanning microscopy. Added into the cell dishes, both QDs and Tat-QDs adhered to the outer leaflet of the plasma membrane of cells within a few minutes, but the binding amount of Tat-QDs was obviously higher than that of QDs. Then both QDs and Tat-QDs can penetrate into cells, and their cellular contents increased with incubation time but both saturated after 3 hours incubation. However the cellular levels of Tat-QDs were higher than those of QDs, with the ratio of 2.1 (±0.3) times in QGY cells and 1.5 (±0.2) times in MCF7 cells, demonstrating the enhancing effect of Tat conjugation on the intracellular delivery of QDs.     

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.     

叶酸修饰的AgInS2量子点在体外癌细胞成像上的应用

成功制备出高品质的三元AgInS₂量子点。通过配体交换法将油溶性AgInS₂量子点转为水溶性量子点, 通过dBSA修饰水溶性量子点形成配位体壳, 使量子点具有更好的稳定性(4周)。从透射电子显微镜(TEM)观察到dBSA修饰后的量子点的粒径增加, 分散性较好, 并且在可见光区域有明显的光致发光。用叶酸对dBSA-MPA量子点进行修饰, 并通过傅立叶变换红外光谱进行了验证。将得到的FA-dBSA-MPA纳米复合材料应用于能与叶酸受体特异性结合的乳腺癌细胞中, 并在荧光倒置显微镜中检测到量子点成功对乳腺癌细胞进行了标记。与dBSA-MPA量子点相比, 表面被叶酸修饰后的量子点与癌细胞的结合效率显著提高。     

Convenient synthesis of stable silver quantum dots with enhanced photoluminescence emission by laser fragmentation

A new strategy for the facile synthesis of very stable and mono-dispersed silver(Ag) quantum dots(QDs) is developed by laser fragmentation of bulk Ag in water using polysorbate 80 as a dispersing and stabilizing agent. The surfactant plays an important role in the formation of size-controlled Ag nano-structures. The Ag QDs have excellent photo-stability of～ 500 h and enhanced photoluminescence(PL) at 510 nm. This has significant implications for selective and ultrasensitive PL probes. Based on laser fragmentation in the biocompatible surfactant solution, our results have opened up a novel paradigm to obtain stable metal QDs directly from bulk targets. This is a breakthrough in the toxicity problems that arise from standard chemical fabrication.     

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.     

Magnetic nanoparticle-based cancer therapy

Nanoparticles(NPs) with easily modified surfaces have been playing an important role in biomedicine.As cancer is one of the major causes of death,tremendous efforts have been devoted to advance the methods of cancer diagnosis and therapy.Recently,magnetic nanoparticles(MNPs) that are responsive to a magnetic field have shown great promise in cancer therapy.Compared with traditional cancer therapy,magnetic field triggered therapeutic approaches can treat cancer in an unconventional but more effective and safer way.In this review,we will discuss the recent progress in cancer therapies based on MNPs,mainly including magnetic hyperthermia,magnetic specific targeting,magnetically controlled drug delivery,magnetofection,and magnetic switches for controlling cell fate.Some recently developed strategies such as magnetic resonance imaging(MRI) monitoring cancer therapy and magnetic tissue engineering are also addressed.