Chang Shu

Facile synthesis and characterization of water soluble ZnSe/ZnS quantum dots for cellar imaging.

Strong fluorescence and low cytotoxicity ZnSe/ZnS quantum dots (QDs) were synthesized by a facile aqueous phase route. It overcame the defects such as instability and low quantum yield of the quantum dots synthesized by early aqueous phase route. L-Glutathione (GSH) and 3-mercaptopropaonic acid (MPA) were used as mixture stabilizers to synthesize high quality ZnSe/ZnS QDs. The samples were characterized by X-ray diffraction (XRD), high resolution transmission electron microscopy (HRTEM), X-ray photoelectron spectrometry (XPS) and their optical properties were investigated by using UV-vis spectrophotometer, fluorescence spectrophotometer (FL), IR spectrophotometer and confocal laser scanning microscope. The synthesized ZnSe/ZnS QDs illuminated blue fluorescence under ultraviolet lamp. Its water-soluble property is excellent and the fluorescence intensity of ZnSe/ZnS QDs almost did not change after 4 months at room temperature. The average diameter of ZnSe/ZnS nanocrystals is about 3 nm and quantum yield (QY) could reach to 70.6% after repeat determination. Low cytotoxicity was ensured by investigated SCG7901 and RAW264.7 cells. In comparison with cadmium based nanocrystals, ZnSe/ZnS QDs posed low cytotoxicity. The cells viability remained 96.7% when the QDs concentration was increased to 10 μmol/L. The results in vitro indicate that ZnSe/ZnS QDs-based probes have good stability, low toxicity and biocompatibility for fluorescence imaging in cancer model system.

Encapsulation of 10-Hydroxy Camptothecin in Supramolecular Hydrogel as an Injectable Drug Delivery System

10-Hydroxy camptothecin (HCPT) has been proven to be a cell cycle-specific chemotherapeutic agent, which is a necessary choice to inhibit tumor residue growth and prevent tumor metastasis after surgery. But it suffers from light decomposition, poor solubility, relatively low bioavailability, and some side effects, which are the major obstacles toward its clinical use. Integration of hydrophobic HCPT with hydrophilic hydrogel is a facile approach to change the disadvantageous situation of HCPT. In this study, a novel supramolecular hydrogelator with improved synthetic strategy was triggered by chemical hydrolysis, and then self-assembled to hydrogel. Taking advantage of the high-equilibrium solubility of HCPT in hydrogelator solution, this hydrogel was utilized to load HCPT via encapsulation as an effective carrier. HCPT hydrogels were characterized by several techniques including transmission electronic microscopy, rheology, and UV spectroscopy. In vitro release experiment indicated HCPT hydrogel could maintain long term and sustained release of HCPT at high accumulated rate. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay showed that HCPT hydrogel had an optimized anticancer efficacy. Besides, with prominent physical properties of carrier, HCPT hydrogel possessed satisfactory stability, syringeability, and recoverability, demonstrating itself as a potential localized injectable drug delivery system.

Targeted killing of cancer cells in vivo and in vitro with IGF-IR antibody-directed carbon nanohorns based drug delivery.

Oxidized single-wall carbon nanohorns (oxSWNHs) have shown great potential in drug delivery. The purpose of this study was to design an effective targeted drug delivery system (DDS) based on oxSWNHs, which could carry high dose of drug to tumor sites and improve the therapeutic efficacy with less adverse effects. OxSWNHs incorporated the anticancer drug vincristine (VCR) via physical adsorption, then wrapped DSPE-PEG-IGF-IR monoclonal antibody (mAb) through an amide liker to obtain the drug delivery system, VCR@oxSWNHs-PEG-mAb. The in vitro release behavior study indicated that the DDS had good sustained release and the cumulative release of VCR was 80% at 144h. Compared with free VCR, the tumor targeting drug delivery efficiently enhanced the cytotoxicity in cultured MCF-7 cells in vitro, and afforded higher antitumor efficacy without obvious toxic effects to normal organs in tumor mice in vivo. In addition, the targeted DDS could reduce the toxicity of VCR to the living mice. This study demonstrated that VCR@oxSWNHs-PEG-mAb might be promising for high treatment efficacy with minimal side effects in future cancer therapy.

Fluorescence resonance energy transfer between ZnSe ZnS quantum dots and bovine serum albumin in bioaffinity assays of anticancer drugs.

In the current work, using ZnSe ZnS quantum dots (QDs) as representative nanoparticles, the affinities of seven anticancer drugs for bovine serum albumin (BSA) were studied using fluorescence resonance energy transfer (FRET). The FRET efficiency of BSA-QD conjugates can reach as high as 24.87% by electrostatic interaction. The higher binding constant (3.63×10(7)Lmol(-1)) and number of binding sites (1.75) between ZnSe ZnS QDs and BSA demonstrated that the QDs could easily associate to plasma proteins and enhance the transport efficacy of drugs. The magnitude of binding constants (10(3)-10(6)Lmol(-1)), in the presence of QDs, was between drugs-BSA and drugs-QDs in agreement with common affinities of drugs for serum albumins (10(4)-10(6)Lmol(-1)) in vivo. ZnSe ZnS QDs significantly increased the affinities for BSA of Vorinostat (SAHA), Docetaxel (DOC), Carmustine (BCNU), Doxorubicin (Dox) and 10-Hydroxycamptothecin (HCPT). However, they slightly reduced the affinities of Vincristine (VCR) and Methotrexate (MTX) for BSA. The recent work will not only provide useful information for appropriately understanding the binding affinity and binding mechanism at the molecular level, but also illustrate the ZnSe ZnS QDs are perfect candidates for nanoscal drug delivery system (DDS).

Characterization and cancer cell targeted imaging properties of human antivascular endothelial growth factor monoclonal antibody conjugated CdTe/ZnS quantum dots

High luminescence quantum yield water-soluble CdTe/ZnS core/shell quantum dots (QDs) stabilized with thioglycolic acid were synthesized. QDs were chemically coupled to fully humanized antivascular endothelial growth factor165 monoclonal antibodies to produce fluorescent probes. These probes can be used to assay the biological affinity of the antibody. The properties of QDs conjugated to an antibody were characterized by ultraviolet and visible spectrophotometry, fluorescent spectrophotometry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transmission electron microscopy and fluorescence microscopy. Cell-targeted imaging was performed in human breast cancer cell lines. The cytotoxicity of bare QDs and fluorescent probes was evaluated in the MCF-7 cells with an MTT viability assay. The results proved that CdTe/ZnS QD-monoclonal antibody nanoprobes had been successfully prepared with excellent spectral properties in target detections. Surface modification by ZnS shell could mitigate the cytotoxicity of cadmium-based QDs. The therapeutic effects of antivascular endothelial growth factor antibodies towards cultured human cancer cells were confirmed by MTT assay.

Colorimetric determination of thrombin by exploiting a triple enzyme-mimetic activity and dual-aptamer strategy

AbstractThe article describes a colorimetric assay for the determination of thrombin. It is based on the application of a triple enzyme-mimetic activity and a dual aptamer binding strategy. The triple signal amplification relies on oxidation of the chromogenic enzyme substrate 3,3,5,5-tetramethylbenzidine (TMB) that is catalyzed by composites consisting of graphene oxide (GO), gold/platinum nanoparticles (AuPtNP), and aptamer (Apt15), a G-quadruplex/hemin conjugate. The dual-aptamer target binding strategy is based on the fact that thrombin has two active sites to be recognized by its aptamers (Apt15 and Apt29). Magnetic beads (MBs) were modified with Apt29 (Apt29-MB) and then are bound by the GO-AuPtNP-Apt15/G-quadruplex/hemin composites. In the presence of thrombin, Apt29-MB and the GO-AuPtNP-Apt15/G-quadruplex/hemin composites form a sandwich-like superstructure. Thus, the absorbance increases due to the formation of TMB oxide produced by catalysis of the composites. Under optimized conditions, the absorbance at 450 nm increases linearly in the 0.30 to 100 nM thrombin concentration range, and the limit of detection is 0.15 nM. The method is simple, rapid, and does not require complicated instrumentation. Bovine serum albumin, human serum albumin and other proteins were found not to interfere. Graphical abstractSchematic presentation of the photometric thrombin assay based on a triple enzyme-mimetic activity of combined nanomaterials (consisting of GO, AuPtNPs and the G-quadruplex/hemin DNAzyme) and two aptamers TMB: 3,3,5,5-tetramethylbenzidine, TMBox: 3,3,5,5-tetramethylbenzidine oxide, AuPtNP: gold/platinum nanoparticles).

Using a peptide segment to covalently conjugate doxorubicin and taxol for the study of drug combination effect

Doxorubicin (Dox) and Taxol can be covalently bonded to the same peptide segment via proper structural modification. Doxorubicin-maleimide derivative links to peptide via Michael addition reaction and Taxol-Succi-NHS active ester connects to the same peptide backbone through ester–amide exchange reaction. Enzymatic transformation, as an inherent biological process, is applied here to trigger the formation of nanofiber networks from the as prepared hydrogelator precursor. The precursor which loads equal molar ratio of Dox and Taxol can self-assemble to form a red stable hydrogel after dephosphorylation reaction catalyzed by alkaline phosphatase (ALP). This hydrogel could maintain sustained release of drugs and show strong anticancer effect. This work, as a new strategy to build a co-delivery system of covalently linked Dox and Taxol, owns the potential to serve as an injectable hydrogel for therapeutic applications.

Self-assembly hydrogels as multifunctional drug delivery of paclitaxel for synergistic tumour-targeting and biocompatibility in vitro and in vivo

In this work, we designed the self‐assembly peptide hydrogels to multiply therapeutic agents for improving anticancer effect and lowering adverse reaction of paclitaxel (PTX).

Effects of paclitaxel (PTX) prodrug-based self-assembly peptide hydrogels combined with suberoylanilide hydroxamic acid (SAHA) for PTX-resistant cancer and synergistic antitumor therapy

In this work, we designed a self-assembly peptide hydrogel encapsulated paclitaxel (PTX) and suberoylanilide hydroxamic acid (SAHA) for cancer co-delivery (Nap–PTX–SAHA). The hydrogels exhibited uniform nanofibers that entangle to form stable networks and pore microstructures (about 140–180 nm) resulting in absorption and storage of hydrophobic drugs. The circular dichroism (CD) spectra of hydrogels exhibit β-turn-like features. Nap–PTX–SAHA hydrogels achieved control over different types of drugs loading and released by diffusion and relaxation processes. Hydrogels exhibited better therapeutic effect and greater synergetic effect compared to the free drugs in vitro and in vivo. Injection of the hydrogels appears to achieve long-term drug release with higher efficacy and better biocompatibility than free drugs. As for the drug biodistribution studies in tumor-bearing mice, the PTX and SAHA from Nap–PTX–SAHA gels uptake in liver, lung and tumor were more than that of free PTX and SAHA. In comparison with free PTX or SAHA, the Nap–PTX–SAHA gels lower the uptake of released drug significantly in the heart, spleen, and kidney to reduce the cardiotoxicity and renaltoxicity. In conclusion, the Nap–PTX–SAHA gels certainly reduce the side effects of PTX and SAHA, enhance synergistic anticancer effects and suppress the drug resistance of PTX. This strategy can be a basis for designing appropriate clinical trials and will hold promise in nanomedicine for different drug combinations.

Dual-function fluorescent probe for cancer imaging and therapy.

To date, several fluorescent probes modified by a single targeting agent have been explored. However, studies on the preparation of dual-function quantum dot (QD) fluorescent probes with dual-targeting action and a therapeutic effect are rare. Here, a dual-targeting CdTe/CdS QD fluorescent probe with a bovine serum albumin-glycyrrhetinic acid conjugate and arginine-glycine-aspartic acid was successfully prepared that could induce the apoptosis of liver cancer cells and showed enhanced targeting in in vitro cell imaging. Therefore, the as-prepared fluorescent probe in this work is an efficient diagnostic tool for the simultaneous detection of liver cancer and breast cancer cells.