Chunhui Wu

Synergistic cytotoxic effect of different sized ZnO nanoparticles and daunorubicin against leukemia cancer cells under UV irradiation.

Failure of chemotherapy to the malignant tumor is usually induced by multidrug resistance (MDR). The development of anti-MDR agents for efficient drug delivery is of great importance in cancer therapy. Recent reports have demonstrated that some anticancer drugs could be readily self-assembled on some biocompatible nanomaterials covalently or non-covalently, which could effectively afford the sustained drug delivery for the target cancer cells and reduce the relevant toxicity towards normal cells and tissues. Thus these biocompatible nanomaterials may play an important role in the relevant biological and biomedical system. In this paper, we have explored the cytotoxic effect of anticancer drug daunorubicin on leukemia cancer cells in the absence and presence of different sized ZnO nanoparticles via fluorescence microscopy, UV-Vis absorption spectroscopy, electrochemical analysis as well as MTT assay. Meanwhile, the cytotoxicity suppression of daunorubicin together with different sized ZnO nanoparticles in the absence and presence of UV irradiation on leukemia cancer cells were also investigated using MTT assay. The results indicate that the combination of the different sized ZnO nanoparticles and daunorubicin under UV irradiation could have synergistic cytotoxic effect on leukemia cancer cells, indicating the great potential of ZnO nanoparticles in relevant clinical and biomedical applications.

Poly(lactic acid) (PLA) based nanocomposites?a novel way of drug-releasing

In this communication, poly(lactic acid) nanofibers have been fabricated by electrospinning and then poly(lactic acid) (PLA) based nanocomposites have been prepared by accumulating anticancer drug daunorubicin on PLA nanofibers combined with TiO2 nanoparticles. Our atomic force microscopy (AFM) and laser-scanning confocal microscope (LSCM) studies demonstrate that the respective drug molecules could be readily self-assembled on the surface of the blends of nano-TiO2 with PLA polymer nanocomposites, which could further efficiently facilitate the drug permeation and accumulation on the target leukemia K562 cells. Besides, the respective new nanocomposites have good biocompatibility, ease of surface chemistry modification and very high surface area, which may afford the possibility for their promising application in pharmacology and biomedical engineering areas.

Novel Nanocomposite of Nano Fe3O4 and Polylactide Nanofibers for Application in Drug Uptake and Induction of Cell Death of Leukemia Cancer Cells

Novel nanocomposites of polylactide (PLA) nanofibers and tetraheptylammonium-capped Fe3O4 magnetic nanoparticles have been prepared and utilized to realize the efficient accumulation of anticancer drug daunorubicin in target cancer cells. The observations of optical microscopy and confocal fluorescence microscopy indicate that the PLA nanofibers and Fe3O4 nanoparticles may contribute to their beneficial effects on intracellular drug uptake of leukemia K562 cell lines in which the efficiently enhanced accumulation of anticancer drug daunorubicin on the membrane of cancer cells could be observed. Meanwhile, the electrochemical detection and the microculture tetrazolium studies were also explored to probe the effect of the relevant nanomaterials on the drug uptake of cancer cells. The results illustrate that the nanocomposites could effectively facilitate the interaction of daunorubicin with leukemia cells and remarkably enhance the permeation and drug uptake of anticancer agents in the cancer cells, which could readily lead to the induction of the cell death of leukemia cells. This observation suggests a new perspective for the targeted therapeutic approaches of cancers.

The incorporation of daunorubicin in cancer cells through the use of titanium dioxide whiskers

Porous nanostructure with its unique properties is found to be able to hold promise in drug delivery. We fabricated the one-dimensional titanium dioxide whiskers (TiO2 Ws) and designed a strategy to explore their drug delivery application and anti-tumor function combined with daunorubicin (DNR). We observed good biocompatibility of TiO2 Ws and noted better photocatalytic activity. In human hepatocarcinoma cells (SMMC-7721 cells), TiO2 Ws can obviously increase the intracellular concentration of DNR and enhance its potential anti-tumor efficiency, indicating TiO2 Ws could produce an efficient drug delivery carrier effect importing DNR into target cells. Furthermore, its photocatalysis further led to the enhanced mortality of cancer cells under UV irradiation. These findings reveal that TiO2 Ws-based delivery of anticancer drugs represents a promising approach in cancer therapy.

Ligand-based neutral ruthenium(II) arene complex: selective anticancer action.

Two new ruthenium(II) arene complexes, 2a (C(24)H(34)B(10)FeRuS(2)) and 2b (C(15)H(26)B(10)O(2)RuS(2)), bearing a carborane unit and other different functional groups were synthesized, and their cytostatic effects on cancerous cells were evaluated. Our observations illustrate that a structural change from a ferrocene unit to a carboxyl group could lead to high selectivity toward cancer cells and facilitate the efficient inhibition of the proliferation of target cells, indicating that the tuning of the overall properties of the ruthenium(II) arene complex by appropriate ligand tagging is critical to creating a selective antineoplastic agent.

Synergistic enhancement effect of magnetic nanoparticles on anticancer drug accumulation in cancer cells

Three kinds of magnetic nanoparticle, tetraheptylammonium capped nanoparticles of Fe(3)O(4), Fe(2)O(3) and Ni have been synthesized, and the synergistic effect of these nanoparticles on the drug accumulation of the anticancer drug daunorubicin in leukaemia cells has been explored. Our observations indicate that the enhancement effect of Fe(3)O(4) nanoparticles is much stronger than that of Fe(2)O(3) and Ni nanoparticles, suggesting that nanoparticle surface chemistry and size as well as the unique properties of the magnetic nanoparticles themselves may contribute to the synergistic enhanced effect of the drug uptake of targeted cancer cells.

New potential anticancer agent of carborane derivatives: selective cellular interaction and activity of ferrocene-substituted dithio-o-carborane conjugates.

The large diversity of structures and unique bonding modes of organometallic complexes make them possible to act as promising candidate therapeutic agents. In this study, the new type of ferrocene-substituted dithio-o-carborane conjugates (FcSB1, FcSB2, and FcSBCO) has been synthesized, and their in vitro antineoplastic activities have been explored by means of the electrochemical study, the real time cell electronic sensing (RT-CES) system, and biological assays. The conjugate-cell interactions were first monitored by electrochemistry, and the results show different cell uptake efficiency for FcSB1, FcSB2, and FcSBCO toward target cells. Both the highly hydrophobic ferrocenyl and carboranyl groups render the conjugates able to rapidly enter cells and exert acute cytotoxicity after 4 h incubation in serum-free media. However, FcSB1, FcSB2, and FcSBCO display different inhibition efficiencies toward SMMC-7721 and HepG2 cancer cells via the G(0)/G(1) arrest mechanism in a physiological environment. The anticancer activity is in the order FcSB2 > FcSB1 > FcSBCO, which is parallel to the order of the redox potentials of the ferrocenyl groups in the three complexes. In particular, FcSB1 and FcSB2 display a potent selective inhibition effect on the proliferation of the cancer cell lines SMMC-7721 and HepG2, but almost no effect on the normal cell line, the human embryonic lung fibroblast (HELF) cells. Thus, these results may provide some clues for use of the ferrocene-carborane conjugates in developing anticancer drugs.

Probing the Dynamic Effect of Cys-CdTe Quantum Dots toward Cancer Cells in Vitro

The application of quantum dots (QDs) in various biomedical areas requires detailed studies of their toxicity. We report a new strategy for probing the biocompatibility of these nanocrystals, namely, a dynamic investigation of cellular uptake images, cell growth curves, metabolic activity changes, and apoptosis aspects of cadmium telluride QDs capped with cysteamine (Cys-CdTe QDs) on human hepatocellular carcinoma SMMC-7721 cells. We used a real-time cell electronic sensing (RT-CES) system in combination with fluorescence microscopy, 3-(4,5-dimethyl-thiazol-zyl)-2,5-diphenyltetrazolium bromide assay, and flow cytometry (FCM) analysis. As observed from fluorescence images and RT-CES system results, Cys-CdTe QDs can readily bind on the cell plasma membrane and then enter into the cancer cell, causing decreased adherence of cancer cells during the initial 6-12 h, while the metabolic activity apparently decreased. After 24 h, the metabolic activity of the cancer cells was significantly reduced, with continued reduction in metabolic activity observed at even longer incubation times. Moreover, FCM observation and DNA fragmentation analysis clearly indicate apoptosis-related phenomena when SMMC-7721 cells were treated with the Cys-CdTe QDs. Thus, our study reveals details of the cellular aging and death process induced by Cys-CdTe QDs.

Synergistic Anticancer Activity of Photo- and Chemoresponsive Nanoformulation Based on Polylysine-Functionalized Graphene

Multimodal therapeutic agents based on nanomaterials for cancer combination therapy have attracted increasing attention. In this report, a novel photo- and chemoactive nanohybrid was fabricated by assembling photosensitizer Zn(II)-phthalocyanine (ZnPc) and anticancer drug doxorubicin (DOX) on the biocompatible poly-l-lysine (PLL)-grafted graphene (G-PLL). This nanocomplex of G-PLL/DOX/ZnPc showed excellent physiochemical properties, including high solubility and stability in biological solutions, high drug loading efficiency, pH-triggered drug release, and ability to generalize (1)O2 under light excitation. Compared to free drug molecules, cells treated with G-PLL/DOX/ZnPc showed a higher cellular uptake. In particular, G-PLL/DOX/ZnPc elicited a remarkable synergistic anticancer activity owing to combined photodynamic and chemotherapeutic effects. The combination dose reduction indexes revealed that combining DOX with ZnPc provided strong synergistic effects (combination index < 0.1) against three cancer cell lines tested (HeLa, MCF-7, and B16). Thus, this study demonstrates programmable dual-modality therapy exemplified by G-PLL/DOX/ZnPc to synergistically treat cancers.

Folate-Functionalized Magnetic-Mesoporous Silica Nanoparticles for Drug/Gene Codelivery To Potentiate the Antitumor Efficacy

An appropriate codelivery system for chemotherapeutic agents and nucleic acid drugs will provide a more efficacious approach for the treatment of cancer. Combining gene therapy with chemotherapeutics in a single delivery system is more effective than individual delivery systems carrying either gene or drug. In this work, we developed folate (FA) receptor targeted magnetic-mesoporous silica nanoparticles for the codelivery of VEGF shRNA and doxorubicin (DOX) (denoted as M-MSN(DOX)/PEI-FA/VEGF shRNA). Our data showed that M-MSN(DOX)/PEI-FA could strongly condense VEGF shRNA at weight ratios of 30:1, and possesses higher stability against DNase I digestion and sodium heparin. In vitro antitumor activity assays revealed that HeLa cell growth was significantly inhibited. The intracellular accumulation of DOX by confocal microscopy and fluorescence spectrophotometry showed that M-MSN(DOX)/PEI-FA were more easily taken up than nontargeted M-MSN(DOX). Quantitative PCR and ELISA data revealed that M-MSN/PEI-FA/VEGF shRNA induced a significant decrease in VEGF expression as compared to cells treated with either the control or other complexes. The invasion and migration phenotypes of the HUVECs were significantly decrease after coculture with MSN/PEI-FA/VEGF shRNA nanocomplexes-treated HeLa cells. The approach provides a potential strategy to treat cancer by a singular nanoparticle delivery system.