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Improved delivery of doxorubicin using rationally designed PEGylated platinum nanoparticles for the treatment of melanoma

机译:使用合理设计的聚乙二醇化铂纳米颗粒治疗黑素瘤,改善阿霉素的递送

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摘要

Efficient delivery of chemotherapeutic drugs to tumor cells is one of the crucial issues for modern day cancer therapy. In this article, we report the synthesis of poly ethylene glycol (PEG) assisted colloidal platinum nanoparticles (PtNPs) by borohydride reduction method at room temperature. PtNPs are stable at room temperature for more than 2 years and are stable in serum and phosphate buffer (pH = 7.4) solution for one week. PtNPs show biocompatibility in different normal cell lines (in vitro) and chicken egg embryonic model (ex vivo). Further, we designed and fabricated PtNPs-based drug delivery systems (DDS: PtNPs-DOX) using doxorubicin (DOX), a FDA approved anticancer drug. Various analytical techniques were applied to characterize the nanomaterials (PtNPs) and DDS (PtNPs-DOX). This DDS exhibits inhibition of cancer cell (B16F10 and A549) proliferation, observed by different in vitro assays. PtNPs-DOX induces apoptosis in cancer cells observed by annexin-V staining method. Intraperitoneal (IP) administration of PtNPs-DOX shows substantial reduction of tumor growth in subcutaneous murine melanoma tumor model compared to control group with free drug. Up-regulation of tumor suppressor protein p53 and down regulation of SOX2 and Ki-67 proliferation markers in melanoma tumor tissues (as observed by immunofluorescence and western blot analysis) indicates probable molecular mechanism for the anticancer activity of DDS. Considering the in vitro and pre-clinical (in vivo) results in murine melanoma, it is believed that platinum nanoparticle-based drug delivery formulation could be exploited to develop an alternative therapeutic nanomedicine for cancer therapy in the near future.
机译:向肿瘤细胞有效递送化疗药物是现代癌症治疗的关键问题之一。在本文中,我们报道了在室温下通过硼氢化物还原法合成聚乙二醇(PEG)辅助的胶体铂纳米颗粒(PtNPs)。 PtNP在室温下稳定2年以上,在血清和磷酸盐缓冲液(pH = 7.4)溶液中稳定1周。 PtNP在不同的正常细胞系(体外)和鸡蛋胚模型(离体)中显示出生物相容性。此外,我们使用FDA批准的抗癌药阿霉素(DOX)设计和制造了基于PtNPs的药物递送系统(DDS:PtNPs-DOX)。应用了各种分析技术来表征纳米材料(PtNPs)和DDS(PtNPs-DOX)。通过不同的体外试验观察到,该DDS表现出对癌细胞(B16F10和A549)增殖的抑制作用。通过膜联蛋白-V染色法观察到,PtNPs-DOX诱导癌细胞凋亡。与具有游离药物的对照组相比,PtNPs-DOX的腹膜内(IP)给药显示皮下鼠黑色素瘤模型中的肿瘤生长显着降低。黑色素瘤肿瘤组织中抑癌蛋白p53的上调以及SOX2和Ki-67增殖标记的下调(通过免疫荧光和蛋白质印迹分析观察到)表明DDS的抗癌活性可能是分子机制。考虑到体外和临床前(体内)导致鼠类黑色素瘤的结果,据信在不久的将来可以开发出基于铂纳米颗粒的药物递送制剂来开发用于癌症治疗的替代性治疗性纳米药物。

著录项

  • 来源
    《Materials science & engineering》 |2020年第3期|110375.1-110375.14|共14页
  • 作者

  • 作者单位

    CSIR Indian Inst Chem Technol Dept Appl Biol Uppal Rd Hyderabad 500007 Telangana India|AcSIR Ghaziabad 201002 India;

    CSIR Indian Inst Chem Technol Dept Appl Biol Uppal Rd Hyderabad 500007 Telangana India;

    CSIR Ctr Cellular & Mol Biol Hyderabad 500007 Telangana India;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Platinum nanoparticles; PEGylated; Melanoma; Drug delivery; Mouse model; Biocompatible;

    机译:铂纳米粒子;聚乙二醇化黑色素瘤药物输送;鼠标模型生物相容性;

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