Chunhui Wu

University of Electronic Science and Technology of China, Chengdu, Sichuan Sheng, China

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Publications (12)45.58 Total impact

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    ABSTRACT: Multimodal therapeutic agents based on nanomaterials for cancer combination therapy have attracted increasing attention. In this report, a novel photo- and chemo-active 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 1O2 under light excitation. Compared to free drug molecules, cells treated with G-PLL/DOX/ZnPc showed a higher cellular uptake. Particularly, 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.
    ACS Applied Materials & Interfaces 11/2014; · 5.90 Impact Factor
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    ABSTRACT: Microbubbles (MBs, usually 2-8 microm) as ultrasound contrast agent and drug carrier are promising for ultrasonic imaging and drug delivery. However, MBs posed some limitations due to their large diameters. In the current study, we developed a nanoscale bubbles (nanobubbles, NBs) by encapsulating the doxorubicin (DOX) into poly(lactic-co-glycolic acid) (PLGA) shells (denoted as DOX-PLGA NBs) for drug delivery into cancer cells. The size, morphology, particle stability, drug encapsulation efficiency, and drug payload were determined. The results showed that the DOX-PLGA NBs were uniform (270 +/- 3 nm) and spherical with a smooth surface, and were well dispersed and stable in water. The encapsulation efficiency and payload of DOX increased with its initial loading concentrations. The release behavior of DOX from the DOX-PLGA NBs exhibited a biphasic pattern characterized by an initial burst release followed by a slower and continuous release at both pH 7.4 and pH 4.4, and also presented in a pH-triggered releasing profile. The qualitative analysis of cellular internalization into HeLa cells by inverted fluorescence microscope showed that the cellular uptake of DOX-PLGA NBs was both concentration- and time-dependent. Moreover, the cell viability was also investigated using CCK-8 assay. It was found that DOX-PLGA NBs showed greater HeLa cell growth inhibition effect in vitro compared with free DOX. It was concluded that the DOX-PLGA NBs were biocompatible and appropriate for anti-cancer drug delivery, and were potentially promising as a new therapeutic system for cancer treatment.
    Journal of Nanoscience and Nanotechnology 04/2014; 14(4):2947-54. · 1.15 Impact Factor
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    ABSTRACT: In this report, the adsorption characteristics and conformation changes of model protein bovine serum albumin (BSA) adsorbed on nanographene oxide (NGO) are described. The adsorption isotherms obtained at pH 4.0, 4.7, 7.4 and 8.8 show that NGO has the highest affinity for BSA in the acid environment of pH 4.0, but the protein adsorption capacity decreases with the pH value increasing. The data imply that the spontaneously binding of BSA to the NGO surfaces is mainly due to the protein conformation and an electrostatic attraction mechanism. The fluorescence and synchronous fluorescence spectroscopic studies show that NGO quenches the fluorescence of BSA both statically and dynamically, and induces obvious perturbations on the conformation of BSA as well as the microenvironments around the Trp and Tyr residues. Moreover, analysis of the secondary structure of the proteins via Fourier transform infrared spectroscopy revealed that evident secondary structural changes may undergo upon adsorption. This study gives an insight into the interaction between NGO and proteins, which is critical in the design of optimal graphene nanosheets-protein conjugates.
    Journal of Nanoscience and Nanotechnology 03/2014; 14(3):2591-8. · 1.15 Impact Factor
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    ABSTRACT: The aberrant activation of Notch-1 signaling pathway has been proven to be associated with the development and progression of cancers. However, the specific roles and the underlying mechanisms of Notch-1 signaling pathway on the malignant behaviors of breast cancer are poorly understood. In this study, using multiple cellular and molecular approaches, we demonstrated that activation of Notch-1 signaling pathway promoted the malignant behaviors of MDA-MB-231 cells such as increased cell proliferation, colony formation, adhesion, migration, and invasion, and inhibited apoptosis; whereas deactivation of this signaling pathway led to the reversal of the aforementioned malignant cellular behaviors. Furthermore, we found that activation of Notch-1 signaling pathway triggered the activation of NF-κB signaling pathway and up-regulated the expression of NF-κB target genes including MMP-2/-9, VEGF, Survivin, Bcl-xL, and Cyclin D1. These results suggest that Notch-1 signaling pathway play important roles in promoting the malignant phenotype of breast cancer, which may be mediated partly through the activation of NF-κB signaling pathway. Our results further suggest that targeting Notch-1 signaling pathway may become a newer approach to halt the progression of breast cancer.
    PLoS ONE 01/2014; 9(4):e95912. · 3.53 Impact Factor
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    ABSTRACT: In gene therapy, how genetic therapeutics can be efficiently and safely delivered into target tissues/cells remains a major obstacle to overcome. To address this issue, nanoparticles consisting of non-covalently coupled polyethyleneimine (PEI) and folic acid (FA) to the magnetic and fluorescent core/shell of Fe3O4@SiO2(FITC) was tested for their ability to deliver Notch-1 shRNA. Our results showed that Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanoparticles are 64 nm in diameter with well dispersed and superparamagnetic. These nanoparticles with on significant cytotoxicity are capable of delivering Notch-1 shRNA into human breast cancer MDA-MB-231 cells with high efficiency while effectively protected shRNA from degradation by exogenous DNaseI and nucleases. Magnetic resonance (MR) imaging and fluorescence microscopy showed significant preferential uptake of Fe3O4@SiO2(FITC)/PEI-FA/Notch-1 shRNA nanocomplex by MDA-MB-231 cells. Transfected MDA-MB-231 cells exhibited significantly decreased expression of Notch-1, inhibited cell proliferation, and increased cell apoptosis, leading to the killing of MDA-MB-231 cells. In light of the magnetic targeting capabilities of Fe3O4@SiO2(FITC)/PEI-FA, our results show that by complexing with a second molecular targeting therapeutic, such as Notch-1 shRNA in this report, Fe3O4@SiO2(FITC)/PEI-FA can be exploited as a novel, non-viral, and concurrent targeting delivery system for targeted gene therapy as well as for MR imaging in cancer diagnosis.
    Scientific reports. 01/2014; 4:7072.
  • Journal of Controlled Release 11/2013; 172(1):e120-1. · 7.63 Impact Factor
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    ABSTRACT: Adhesion of cancer cell to endothelial cells and the subsequent trans-endothelial migration are key steps in hematogenous metastasis. However, the molecular mechanisms of cancer cell/endothelial cell interaction under hemodynamic shear flow and how shear flow-induced cancer cell mechanotransduction are yet to be fully defined. In this study, we identified that the integrins of both platelet glycoprotein IIb/IIIa (GP IIb/IIIa) and αvβ3 were crucial for hematogenous metastasis of human breast carcinoma MDA-MB-231cells. The cell migration and invasion were studied by using Millicell cell culture insert system. The numbers of invaded MDA-MB-231 cells significantly increased by thrombin-activated platelets and reduced by eptifibatide, a platelet inhibitor. Meanwhile, RGDWE peptides, a specific inhibitor of αvβ3 integrin, also inhibited MDA-MB-231 cell invasion. We further used a parallel-plate flow chamber to investigate MDA-MB-231 cell adhesion under flow conditions. Alike in static condition, the adhesion capability of MDA-MB-231 cells to endothelial monolayer was also significantly affected by GP IIb/IIIa and αvβ3 integrins. The expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and αvβ3 integrin in MDA-MB-231 cells were up-regulated after low shear stress exposure (1.84 dynes/cm(2), 2 h). Moreover, we also demonstrated that low shear stress induced a sustained activation of p85 (a regulatory subunit of PI3K) and Akt. Pretreating MDA-MB-231 cells with the specific PI3K inhibitor of LY294002 abolished the shear stress induced-Akt activation, and the expression of MMP-2, MMP-9, vascular endothelial growth factor (VEGF) and αvβ3 integrin were also down-regulated. Immunofluorescence assay showed that low shear stress also induced αvβ3 integrin clustering and nuclear factor-κB (NF-κB) activation. Interestingly, shear stress-induced activation of Akt and NF-κB was attenuated by LM609, a specific antibody of αvβ3 integrin. It suggests that αvβ3 integrin might be as a mechanosensor to trigger both PI3K/Akt and NF-κB signaling pathways. Taken together, these results establish that GP IIb/IIIa and αvβ3 integrins are essential mediators, and provide insight into how shear stress-induced αvβ3 integrin activation and the downstream pathways for contribution to MDA-MB-231 cell adhesion, migration and invasion.
    Cancer letters 10/2013; · 5.02 Impact Factor
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    ABSTRACT: Multifunctional nanomaterials with unique magnetic and luminescent properties have broad potential in biological applications. Because of the overexpression of vascular cell adhesion molecule-1 (VCAM-1) receptors in inflammatory endothelial cells as compared with normal endothelial cells, an anti-VCAM-1 monoclonal antibody can be used as a targeting ligand. Herein we describe the development of multifunctional core-shell Fe3O4@SiO2 nanoparticles with the ability to target inflammatory endothelial cells via VCAM-1, magnetism, and fluorescence imaging, with efficient magnetic resonance imaging contrast characteristics. Superparamagnetic iron oxide and fluorescein isothiocyanate (FITC) were loaded successfully inside the nanoparticle core and the silica shell, respectively, creating VCAM-1-targeted Fe3O4@SiO2(FITC) nanoparticles that were characterized by scanning electron microscopy, transmission electron microscopy, fluorescence spectrometry, zeta potential assay, and fluorescence microscopy. The VCAM-1-targeted Fe3O4@SiO2(FITC) nanoparticles typically had a diameter of 355 ± 37 nm, showed superparamagnetic behavior at room temperature, and cumulative and targeted adhesion to an inflammatory subline of human umbilical vein endothelial cells (HUVEC-CS) activated by lipopolysaccharide. Further, our data show that adhesion of VCAM-1-targeted Fe3O4@SiO2(FITC) nanoparticles to inflammatory HUVEC-CS depended on both shear stress and duration of exposure to stress. Analysis of internalization into HUVEC-CS showed that the efficiency of delivery of VCAM-1-targeted Fe3O4@SiO2(FITC) nanoparticles was also significantly greater than that of nontargeted Fe3O4@SiO2(FITC)-NH2 nanoparticles. Magnetic resonance images showed that the superparamagnetic iron oxide cores of the VCAM-1-targeted Fe3O4@SiO2(FITC) nanoparticles could also act as a contrast agent for magnetic resonance imaging. Taken together, the cumulative adhesion and uptake potential of these VCAM-1-targeted Fe3O4@SiO2(FITC) nanoparticles targeted to inflammatory endothelial cells could be used in the transfer of therapeutic drugs/genes into these cells or for diagnosis of vascular disease at the molecular and cellular levels in the future.
    International Journal of Nanomedicine 01/2013; 8:1897-906. · 4.20 Impact Factor
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    ABSTRACT: Objectives: Technologies to increase tissue vascularity are critically important to the fields of tissue engineering and cardiovascular medicine. Angiogenic factors, like VEGF, have been widely investigated to induce vascular endothelial cell proliferation and angiogenesis for establishing a vascular network. However, effective transport of VEGF gene to target cells with minimal side effects remains a challenge despite the use of unique viral and non-viral delivery approaches. Methods: This study presents a novel gene delivery system of fluorescein isothiocyanate (FITC) doped and poly(allylamine hydrochloride) (PAH) grafted Fe(3)O(4)@SiO(2) nanoparticles, which allows efficient loading of pVEGF to form Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes for VEGF gene delivery and cellular imaging. Results: The nanocomplexes maintain their superparamagnetic property in the silica composites at room temperature, reaching a saturation magnetization value of 5.19 emu/g of material, and no appreciable change in magnetism even after PAH modification. The quantitative analysis of cellular internalization into the living human umbilical vein endothelial cells (HUVECs) demonstrated that the Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes could be entirely internalized by HUVECs, and exhibit high VEGF gene expression and an innocuous toxic profile. The magnetic resonance (MR) images showed that the superparamagnetic iron oxide core of Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes could also act as a contrast agent for MR imaging. This property provides a benefit for monitoring gene delivery. Conclusion: These data highlight multifunctional Fe(3)O(4)@SiO(2)(FITC)/PAH/pVEGF nanocomplexes as an attractive platform for gene delivery of angiogenesis, and also making it a potential candidate of nanoprobes for cellular fluorescent imaging or MR imaging.
    Expert Opinion on Drug Delivery 10/2012; 9(10):1197-207. · 4.87 Impact Factor
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    ABSTRACT: Novel stable core/shell Fe(3)O(4)@SiO(2)/PAH nanoparticles are synthesized using 15 nm Fe(3)O(4) as the template that is modified with PAH. The resulting nanoparticles can absorb plasmid DNA to mediate gene transfer in cultured HeLa cells. An electrophoretic assay suggests that the Fe(3)O(4)@SiO(2)/PAH nanoparticles protect the plasmid DNA from serum and DNase I degradation. A cell viability assay shows that the Fe(3)O(4)@SiO(2)/PAH nanoparticles exhibit a low cytotoxicity toward endothelial cells. Qualitative analysis of transfection in HeLa cells by nanoparticles carrying a plasmid DNA encoding EGFP demonstrates a fairly high expression level, even in the presence of serum. Thus, Fe(3)O(4)@SiO(2)/PAH nanoparticles are biocompatible and suitable for nonviral delivery, and may find applications in cancer therapy.
    Macromolecular Bioscience 11/2011; 11(11):1563-9. · 3.74 Impact Factor
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    ABSTRACT: The expression of certain endothelial cell adhesion molecules is increased during endothelial dysfunction or inflammatory activation. This has led to the concept of using microbubbles for targeted molecular imaging or drug delivery. In this approach, microbubbles with a specific ligand to receptors expressed at the site of specific diseases are constructed. The present study aimed to engineer a novel type of bio-functionalized microbubbles (vascular cell adhesion molecule 1 [VCAM-1]-targeted microbubbles), and determine whether VCAM-1-targeted microbubbles exhibit specific adhesion to lipopolysaccharide (LPS)-activated endothelial cells. Our data showed that VCAM-1 expression was significantly upregulated in both LPS-activated endothelial cells in vitro and endothelium in a rat atherosclerosis model in vivo. Targeted microbubbles were designed by conjugating anti-VCAM-1 monoclonal antibodies to the shell of microbubbles using biotin-avidin bridging chemistry methods. Microbubble adhesion to endothelial cells was assessed in a flow chamber at two shear stress conditions (6.3 and 10.4 dynes/cm²). Our data showed that microbubble adhesion depends on both the surface anti-VCAM-1 antibody densities and the exposed shear stresses. Adhesion of VCAM-1-targeted microbubbles onto LPS-activated endothelial cells increased with the surface antibody densities, and decreased with the exposed shear stresses. These findings showed that the specific ligand-carrying microbubbles have considerable potential in targeted ultrasound molecular imaging or ultrasound-assisted drug/gene delivery applications.
    International Journal of Nanomedicine 01/2011; 6:2043-51. · 4.20 Impact Factor
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    ABSTRACT: Multifunctionalized nanoparticles (NPs) are emerging as ideal tools for gene/drug delivery, bioimaging, labeling, or intracellular tracking in biomedical applications, and have attracted considerable attention owing to their unique advantages. In this study, fluorescent silica NPs were synthesized by a modified Stöber method using conjugates of 3-mercaptopropyltrimethoxysilane (MPS) and maleimide-fluorescein isothiocyanate (maleimide-FITC). Mean diameters of the NPs were controlled between 212-2111 nm by regulating MPS concentration in the reaction mixture. Maleimide-FITC molecules were doped into NPs or conjugated to the surface of NPs through the chemical reaction of maleimide and thiol groups. The data showed that the former NPs are better than the latter by comparing their fluorescence intensity. Furthermore, folate molecules were linked to the FITC-doped silica NPs by using polyethylene glycol (PEG) (NH2-PEG-maleimide) as a spacer, thus forming folate receptor targeting fluorescent NPs, referred to as NPs(FITC)-PEG-Folate. The quantitative analysis of cellular internalization into different cancer cells showed that the delivery efficiency of KB cells (folate receptor-positive cells) is more than six-fold higher than that of A549 cells (folate receptor-negative cells). The delivery efficiency of KB cells decreased significantly after free folate addition to the cell culture medium because the folate receptors were occupied by the free folate. The NPs endocytosis mechanism was also investigated. It was shown that clathrin, an inhibitor of cell phagocytosis, markedly decreased the NPs uptake into KB cells, suggesting that it plays an important role in NPs cellular internalization. These results demonstrated that the novel particles of NPs(FITC)-PEG-Folate are promising for fluorescent imaging or targeting delivery to folate receptor-positive tumors.
    International Journal of Nanomedicine 01/2011; 6:2023-32. · 4.20 Impact Factor

Publication Stats

37 Citations
45.58 Total Impact Points

Institutions

  • 2011–2013
    • University of Electronic Science and Technology of China
      • School of Life Science and Technology
      Chengdu, Sichuan Sheng, China