Zhiting Deng

Chinese Academy of Sciences, Peping, Beijing, China

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Publications (7)23.93 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We demonstrate that a surface acoustic wave at tens of megahertz frequency is capable of inducing microbubble cluster destruction at a desired location to achieve a single cell's reparable sonoporation. By controlling the position of the microbubble cluster relative to the targeted cell precisely, the effective size of the collapsing microbubbles is measured to be less than 0.68 times the diameter of microbubble cluster. Furthermore, the sonoporation efficiency and the cell viability are 82.4% ± 6.5% and 90% ± 8.7%, respectively, when the targeted cell is within the effective microbubble destruction region.
    01/2014; 104(7).
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    ABSTRACT: The circumvention of multidrug resistance (MDR) plays a critically important role in the success of chemotherapy. The aim of this work is to investigate the effectiveness and possible mechanisms of the reversal of MDR phenotype in human breast cancer cells by using doxorubicin-liposome-microbubble complexes (DLMC) assisted by ultrasound (US). DLMC is fabricated through conjugating doxorubicin (DOX)-liposome (DL) to the surface of microbubbles (MB) via the biotin-avidin linkage. The resulting drug-loaded complexes are then characterized and incubated with MCF-7/ADR human breast cancer cells and followed by US exposure. Our results show the more rapid cellular uptake, evident enhancement of nuclear accumulation and less drug efflux in the resistant cells treated by DLMC+US than those treated by DL, DL+verapamil under the same US treatment or DLMC without US. The enhanced drug delivery and cellular uptake also associated with increase of cytotoxicity against MCF-7/ADR cells, lower MCF-7/ADR cell viability and higher apoptotic cells. Mechanism investigations further disclose a significant increase of reactive oxygen species (ROS) level, enhanced DNA damage and obvious reduction of P-glycoprotein expression in the resistant cells treated with DLMC+US compared with the control cases of cells treated by DLMC, DL+US or DL+verapamil+US. In conclusion, our study demonstrates that DLMC in combination with US may provide an effective delivery of drug to sensitize cells to circumvent MDR and to enhance the therapeutic index of the chemotherapy.
    Journal of Controlled Release 11/2013; · 7.63 Impact Factor
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    ABSTRACT: Liposome-microbubble complexes (LMC) have become a promising therapeutic carrier for ultrasound-triggered drug delivery to treat malignant tumors. However, the efficacy for ultrasound-assisted chemotherapy in vivo and the underlying mechanisms remain to be elucidated. Here, we investigated the feasibility of using paclitaxel-liposome-microbubble complexes (PLMC) as possible ultrasound (US)-triggered targeted chemotherapy against breast cancer. PTX-liposomes (PL) were conjugated to the microbubble (MB) surface through biotin-avidin linkage, increasing the drug-loading efficiency of MBs. The significant increased release of payloads from liposome-microbubble complexes were achieved upon US exposure. We used fluorescent quantum dots (QDs) as a model drug to show that released QDs were taken up by 4T1 breast cancer cells treated with QD-liposome-microbubble complexes (QLMC) and US, and uptake depended on the exposure time and intensity of insonication. We found that PLMC plus US inhibited tumor growth more effectively than PL plus US or PLMC without US, not only in vitro, but also in vivo. Histologically, the inhibition of tumor growth appeared to result from increased apoptosis and reduced angiogenesis in tumor xenografts. In addition, a significant increase of drug concentration in tumors was observed in comparison to treatment with non-conjugated PL or PLMC without US. The significant increase in antitumor efficacy of PLMC plus US suggests their potential use as a new targeted US chemotherapeutic approach to inhibit breast cancer growth.
    Journal of Controlled Release 01/2013; · 7.63 Impact Factor
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    ABSTRACT: A novel cationic microbubble (MB) for improvement of the DNA loading capacity and the ultrasound-mediated gene delivery efficiency has been developed; it has been prepared with commercial lipids and a stearic acid modified polyethylenimine 600 (Stearic-PEI600) polymer synthesized via acylation reaction of branched PEI600 and stearic acid mediated by N, N'-carbonyldiimidazole (CDI). The MBs' concentration, size distribution, stability and zeta potential (ζ-potential) were measured and the DNA loading capacity was examined as a function of the amount of Stearic-PEI600. The gene transfection efficiency and cytotoxicity were also examined using breast cancer MCF-7 cells via the reporter plasmid pCMV-Luc, encoding the firefly luciferase gene. The results showed that the Stearic-PEI600 polymer caused a significant increase in magnitude of ζ-potential of MBs. The addition of DNA into cationic MBs can shift ζ-potentials from positive to negative values. The DNA loading capacity of the MBs grew linearly from (5±0.2) ×10(-3) pg/µm(2) to (20±1.8) ×10(-3) pg/µm(2) when Stearic-PEI600 was increased from 5 mol% to 30 mol%. Transfection of MCF-7 cells using 5% PEI600 MBs plus ultrasound exposure yielded 5.76±2.58×10(3) p/s/cm(2)/sr average radiance intensity, was 8.97- and 7.53-fold higher than those treated with plain MBs plus ultrasound (6.41±5.82) ×10(2) p/s/cm(2)/sr, (P<0.01) and PEI600 MBs without ultrasound (7.65±6.18) ×10(2) p/s/cm(2)/sr, (P<0.01), respectively. However, the PEI600 MBs showed slightly higher cytotoxicity than plain MBs. The cells treated with PEI600-MBs and plain MBs plus ultrasound showed 59.5±6.1% and 71.4±7.1% cell viability, respectively. In conclusion, our study demonstrated that the novel cationic MBs were able to increase DNA loading capacity and gene transfection efficiency and could be potentially applied in targeted gene delivery and therapy.
    PLoS ONE 01/2013; 8(9):e76544. · 3.73 Impact Factor
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    ABSTRACT: Multidrug resistance (MDR) in cancer cells is a significant obstacle to successful cancer therapy. Doxorubicin (DOX) is very active chemotherapeutic agent for the treatment of breast cancer and the efficacy of DOX is also restricted by multidrug resistance.Ultrasound (US) targeted destruction of drug loaded microbubbles (MBs) is gaining more and more attention as a promising strategy for locally drug delivery. In this article, through avidinbiotin binding of DOX-containing liposomes to the microbubbles, we developed DOX-liposome-containing microbubbles in order to investigate its effect of enhancing cellular uptake and cytotoxicity of DOX against drug-resistant cancer cells. The results demonstrated that treatment of cells with ultrasound and DOX-liposome-containing microbubbles caused a significant higher drug uptake in DOX-resistant MCF-7 cells, compared with control (DOX-liposome). More importantly, a significant enhancement of tumor growth inhibition against DOX-resistant MCF-7 cells was found when using the drug-liposome-containing microbubbles combined with ultrasound.Compared with DOX-liposome treatment, the cytotoxicity effect was greatly enhanced from 21% to 60%. By further mechanism study, DOX-loaded microbubbles plus ultrasound induced significant apoptosis in MDR line of MCF-7 cells.
    The Journal of the Acoustical Society of America 04/2012; 131(4):3366. · 1.65 Impact Factor
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    ABSTRACT: The aim of this study was to assess the properties of a new designed cationic microbubbles as gene carriers and the relative gene transfection efficacy with ultrasound triggered microbubble destruction. Polyethylenimine as a high efficient gene transfection agent has higher cell toxicity with molecular weight increasing. Stearic acid was used to modify branched polyethylenimine to change its hydrophilic properties so that it can be assembled onto the lipid shell of the microbubbles and simultaneously decrease its cell toxicity. Cationic microbubbles was prepared by encapsulating perfluoropropane into phospholipids and stearic acid modified polyethylenimine hybrid shell using mechanical vibration method. The mean, median size and zeta potential of the microbubbles were measured 1.841.62um, 1.60um and 54mv respectively. Hoechst 33258 was used to stain the green fluorescent protein reporter plasmid which was charge-coupled to cationic microbubbles, and microbubbles was observed emitting blue light under a fluorescence microscope. About 4ug plasmid loaded by 10(8) microbubles that contain 5% mole ratio stearic acid modified polyethylenimine was measured by gel electrophoresis. A 1.25MHz single element transducer was used to mediate the gene transfection to MCF-7 cell by using the cationic microbubbles and enhancement of green fluorescent protein expression was observed.
    The Journal of the Acoustical Society of America 04/2012; 131(4):3366. · 1.65 Impact Factor
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    ABSTRACT: The aim of this work was to develop paclitaxel-liposome loaded microbubbles (PTX-loaded MBs) and to investigate the efficacy of chemotherapy through ultrasound-triggered drug delivery in vitro and in vivo. PTX-loaded liposomes were prepared by a minor modification of thin film hydration method and further conjugated to the surface of microbubbles through biotin-avidin linkage. The resulting payload-loaded MBs were characterized and applied to ultrasound assisted chemotherapy in breast cancer. Our results showed the MBs were able to achieve satisfactory drug encapsulation efficiency. Under ultrasound exposure, about 9.54-fold higher drug release and a significant improvement of cell uptake than that of loaded liposomes were observed. In addition, PTX-loaded MBs showed significantly greater tumor growth inhibition both in vitro and in vivo xenograft growth of breast tumor cells, compared with PTX-loaded liposomes and unloaded MBs. Drug distributions assay in various organs (heart, liver, spleen, lung, kidney and tumor) indicated about 3-fold higher PTX enriched in tumor. Histological examinations further demonstrated the tumor growth inhibition might contribute to increased apoptosis and reduced angiogenesis in tumor xenografts. In conclusion, the study indicated the PTX-loaded MBs significantly increased the anti-tumor efficacy and can be used as a potential chemotherapy approach for ultrasound assisted breast cancer treatment.
    The Journal of the Acoustical Society of America 04/2012; 131(4):3366. · 1.65 Impact Factor

Publication Stats

9 Citations
23.93 Total Impact Points

Institutions

  • 2013–2014
    • Chinese Academy of Sciences
      • Institute of Biomedical Engineering and Health Technology
      Peping, Beijing, China
  • 2012–2013
    • Northeast Institute of Geography and Agroecology
      • Institute of Biomedical Engineering and Health Technology
      Beijing, Beijing Shi, China
    • University Town of Shenzhen
      Shen-ch’üan-shih, Zhejiang Sheng, China