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Analyzing Liposomal Drug Delivery Systems in Three-Dimensional Cell Culture Models Using MALDI Imaging Mass Spectrometry

机译:使用MALDI成像质谱法分析三维细胞培养模型中的脂质体药物递送系统

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摘要

Cancer chemotherapeutics often fail to reach all diseased cells. To help solve this problem, researchers are investigating novel drug delivery systems. Liposomes are an attractive Option due to their low toxicity, high biocompatibility, and potential to carry a large amount of a drug to the tumor site, all while avoiding being eliminated from the body. This study evaluates the penetration of doxorubicin-encased liposomes into three-dimensional cell cultures, or spheroids. Liposomes composed of lipids containing head groups of phosphatidylcholine (PC), phosphatidylethanolamine (PE), and cholesterol were created by extrusion. Doxorubicin is encapsulated within the hydrophilic core of the liposome. The drug is actively released in the spheroid as the lipids bind to cellular lipid bilayers. Spheroids were dosed with liposomal doxorubicin, free doxorubicin, or media control to assess drug distribution over the course of 72 h. Drug penetration was visualized by Matrix-Assisted Laser Desorption/Ionization-Imaging Mass Spectrometry,(MALDI-IMS) with confirmation by steady state fluorescence microscopy, creating a comprehensive picture of drug distribution. This technique is able to identify both free and liposomal doxorubicin throughout the spheroid after just 12 hours of treatment. Additionally, MALDI IMS is able to detect three metabolites of doxorubicin, indicating that cells actively metabolize the drug during treatment. Steady state fluorescence microscopy cannot distinguish the drug from its metabolites as they have the same emission spectra. This report summarizes the first study to use MALDI IMS to analyze drug penetration of a liposomal drug carrier as well as its metabolites.
机译:癌症化学治疗剂经常无法到达所有患病细胞。为了帮助解决这个问题,研究人员正在研究新的药物递送系统。由于它们的低毒性,高生物相容性和将大量药物携带到肿瘤部位的可能性,脂质体是一种吸引力的选择,同时避免被从身体中消除。该研究评估了将多柔比星包装脂质体的渗透到三维细胞培养物中或球状体。通过挤出产生由含有磷脂酰胆碱(PC),磷脂酰乙醇胺(PE)和胆固醇的脂质组成的脂质组成的脂质体。多柔比星被封装在脂质体的亲水核心内。当脂质与细胞脂双层结合时,该药物在球状体中被主动释放。用脂质体DOXORUBICIN,自由多柔比星或培养基对照给药,以评估72小时的药物分布。通过基质辅助激光解吸/电离成像质谱法(MALDI-IMS)通过稳态荧光显微镜进行确认,形成药物渗透,从而形成了药物分布的全面图像。该技术能够在仅需12小时的处理后在整个球状体中识别自由和脂质体的多柔比星。此外,MALDI IMS能够检测多柔比星的三种代谢物,表明细胞在治疗过程中激活了药物的性能。稳态荧光显微镜不能像具有相同的发射光谱一样将药物与其代谢物区分开。本报告总结了第一次使用MALDI IMS分析脂质体药物载体的药物渗透以及其代谢物的研究。

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  • 来源
    《Analytical chemistry》 |2017年第16期|共6页
  • 作者单位

    Univ Notre Dame Harper Canc Res Inst Dept Chem &

    Biochem 152 McCourtney Hall Notre Dame IN 46556 USA;

    Univ Notre Dame Harper Canc Res Inst Dept Chem &

    Biochem 152 McCourtney Hall Notre Dame IN 46556 USA;

    Univ Notre Dame Harper Canc Res Inst Dept Chem &

    Biochem 152 McCourtney Hall Notre Dame IN 46556 USA;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分析化学;
  • 关键词

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