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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Nanoparticle-mediated targeting of MAPK signaling predisposes tumor to chemotherapy
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Nanoparticle-mediated targeting of MAPK signaling predisposes tumor to chemotherapy

机译：纳米粒子介导的MAPK信号转导使肿瘤易于化疗

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摘要

The MAPK signal transduction cascade is dysregulated in a majority of human tumors. Here we report that a nanoparticle-mediated targeting of this pathway can optimize cancer chemotherapy. We engineered nanoparticles from a unique hexadentate-polyD,L-lactic acid-co-glycolic acid polymer chemically conjugated to PD98059, a selective MAPK inhibitor. The nanoparticles are taken up by cancer cells through endocytosis and demonstrate sustained release of the active agent, resulting in the inhibition of phosphor-ylation of downstream extracellular signal regulated kinase. We demonstrate that nanoparticle-mediated targeting of MAPK inhibits the proliferation of melanoma and lung carcinoma cells and induces apoptosis in vitro. Administration of the PD98059-nanoparticles in melanoma-bearing mice inhibits tumor growth and enhances the antitumor efficacy of cisplatin chemotherapy. Our study shows the nanoparticle-mediated delivery of signal transduction inhibitors can emerge as a unique paradigm in cancer chemotherapy.
机译：MAPK信号转导级联在大多数人类肿瘤中均失调。在这里，我们报告纳米粒子介导的这种途径的靶向可以优化癌症化疗。我们设计了一种独特的六齿-polyD，L-乳酸-乙醇酸共聚体，与一种选择性的MAPK抑制剂PD98059化学偶联而成的纳米颗粒。纳米颗粒通过内吞作用被癌细胞吸收，并显示出活性剂的持续释放，从而抑制了下游细胞外信号调节激酶的磷酸化。我们证明纳米粒子介导的靶向MAPK抑制黑素瘤和肺癌细胞的增殖并诱导体外凋亡。在荷黑素瘤小鼠中施用PD98059纳米颗粒可抑制肿瘤生长并增强顺铂化疗的抗肿瘤功效。我们的研究表明，纳米粒子介导的信号转导抑制剂的传递可以作为癌症化学疗法的独特范例。

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    Sudipta Basu; Rania Harfouche; Shivani Soni; Geetanjali Chimote; Raghunath A. Mashelkar; Shiladitya Sengupta;

  • 作者单位

    Harvard-MIT Division of Health Sciences and Technology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;

    Harvard-MIT Division of Health Sciences and Technology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;

    Harvard-MIT Division of Health Sciences and Technology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;

    Harvard-MIT Division of Health Sciences and Technology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;

    Harvard-MIT Division of Health Sciences and Technology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115 National Chemical Laboratories, Pune 411008, India;

    Harvard-MIT Division of Health Sciences and Technology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    cancer; signal transduction;

    机译：癌症;信号转导;

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