Xiaojing Zhang

Cross Cancer Institute, Edmonton, Alberta, Canada

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Publications (3)7.25 Total impact

  • Quanrong Gu · James Z Xing · Min Huang · Xiaojing Zhang · Jie Chen
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    ABSTRACT: Paclitaxel is a microtubule inhibitor causing mitotic arrest and is widely used in cancer chemotherapy. However, its poor water solubility restricts its direct clinical applications. In this article, we report paclitaxel-loaded nanoparticles that are water soluble and that can improve the drug's bio-distribution and therapeutic efficacy. Paclitaxel-loaded nanoparticles were synthesized by using Pluronic copolymers (F-68 and P-123) and surfactant (Span 40) as nanocarrier. The toxicity and cellular uptake of paclitaxel-loaded nanoparticles were evaluated. The paclitaxel-loaded nanoparticles can completely disperse into phosphate buffer saline to produce a clear aqueous suspension. Based on HPLC analysis, the drug-loading rate is 9.0 ± 0.1% while drug encapsulation efficiency is 99.0 ± 1.0%. The cytotoxicity assay was performed using breast cancer MCF-7 and cervical cancer Hela cells. For MCF-7 cells, the half maximal inhibitory concentrations (IC(50)) of paclitaxel-loaded nanoparticles and paclitaxel are 8.5 ± 0.3 and 14.0 ± 0.7 ng/mL at 48 hours and 3.5 ± 0.4 and 5.2 ± 0.5 ng/mL at 72 hours across several runs. IC(50) of paclitaxel-loaded nanoparticles and paclitaxel for Hela cells are 5.0 ± 0.3 and 8.0 ± 0.3 ng/mL at 48 hours and 2.0 ± 0.1 and 6.5 ± 0.3 ng/mL at 72 hours. In-vitro studies show that the drug's nanoformulation gives obvious enhancements in the drug's efficiency at killing cancer cells over paclitaxel alone. Materials of the nanocarrier used for nanoformulation are approved with low toxicity according to the result of cell studies. Conclusion: paclitaxel-loaded nanoparticles greatly improved the physicochemical properties of paclitaxel without modifying its chemical structure, allowing for deep-site cancer drug delivery and enhancing the drug therapeutic efficiency.
    No preview · Article · May 2012 · Journal of Biomaterials Applications
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    ABSTRACT: Glucose-capped gold nanoparticles (Glu-GNPs) have been used to improve cellular targeting and radio-sensitization. In this study, we explored the mechanism of Glu-GNP enhanced radiation sensitivity in radiation-resistant human prostate cancer cells. Cell survival and proliferation were measured using MTT and clonogenic assay. Flow cytometry with staining by propidium iodide (PI) was performed to study the cell cycle changes induced by Glu-GNPs, and western blotting was used to determine the expression of p53 and cyclin proteins that correlated to cell cycle regulation. With 2 Gy of ortho-voltage irradiation, Glu-GNP showed a 1.5-2.0 fold enhancement in growth inhibition when compared to x-rays alone. Comparing the cell cycle change, Glu-GNPs induced acceleration in the G0/G1 phase and accumulation of cells in the G2/M phase at 29.8% versus 18.4% for controls at 24 h. G2/M arrest was accompanied by decreased expression of p53 and cyclin A, and increased expression of cyclin B1 and cyclin E. In conclusion, Glu-GNPs trigger activation of the CDK kinases leading to cell cycle acceleration in the G0/G1 phase and accumulation in the G2/M phase. This activation is accompanied by a striking sensitization to ionizing radiation, which may have clinical implications.
    Full-text · Article · Oct 2009 · Nanotechnology
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    ABSTRACT: Nanotechnology is an emerging field with significant translational potential in medicine. In this study, we applied gold nanoparticles (GNP) to enhance radiation sensitivity and growth inhibition in radiation-resistant human prostate cancer cells. Gold nanoparticles (GNPs) were synthesized using HAuCl4 as the gold particle source and NaBH4 as the reductant. Either thio-glucose or sodium citrate was then added to the solution separately to bind the GNPs to form thio-glucose-capped gold nanoparticles (Glu-GNP) and neutral gold nanoparticles (TGS-GNPs). Human prostate carcinoma DU-145 cells were exposed to vehicle, irradiation, 15nM TGS-GNPs, or 15nM Glu-GNPs, or GNPs plus irradiation. The uptake assays of GNP were performed using hemocytometer to count cells and the mass spectrometry was applied to calculate gold mass. The cytotoxicity induced by GNPs, irradiation, or GNPs plus irradiation was measured using a standard colorimetric MTT assay. Exposure to Glu-GNPs resulted in a three times increase of nanoparticle uptake compared to that of TGS-GNPs in each target cell (p < 0.005). Cytoplasmic intracellular uptake of both TGS-GNPs and Glu-GNPs resulted in a growth inhibition by 30.57% and 45.97% respectively, comparing to 15.88% induced by irradiation alone, in prostate cancer cells after exposure to the irradiation. Glu-GNPs showed a greater enhancement, 1.5 to 2 fold increases within 72 hours, on irradiation cytotoxicity compared to TGS-GNPs. Tumour killing, however, did not appear to correlate linearly with nanoparticle uptake concentrations. These results showed that functional glucose-bound gold nanoparticles enhanced radiation sensitivity and toxicity in prostate cancer cells. In vivo studies will be followed to verify our research findings.
    No preview · Article · Jun 2008 · Clinical and investigative medicine. Medecine clinique et experimentale