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首页> 外文期刊>Biomaterials Science >Attempts to strengthen and simplify the tumor vascular normalization strategy using tumor vessel normalization promoting nanomedicines
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Attempts to strengthen and simplify the tumor vascular normalization strategy using tumor vessel normalization promoting nanomedicines

机译：试图利用肿瘤血管标准化促进纳米型林分的肿瘤血管标准化策略

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摘要

Tumor vascular normalization theory opened the door for the rational use of antiangiogenic agents and chemotherapeutics. However, efforts to seize the normalization window have constrained the development of vascular normalization therapy in clinical applications owing to the lack of circulating biomarkers and the tedious dosage regimes. Applying Occam's Razor to therapeutic design inspired us to construct an effective and simple tumor vascular normalization prompting strategy. Herein, we developed tumor vessel normalization prompting nanomedicine lipid derivative conjugates (LGCs) made of anti-angiogenic agents with low molecular weight heparin (LMWH) and gemcitabine (Gem). This treatment exploits the complementary action of anti-vascular endothelial growth factor (VEGF) therapy and metronomic chemotherapy (MET) to strengthen the tumor vascular normalization effect. Furthermore, by loading cytotoxic drugs, such as paclitaxel (PTX), into the LGCs we constructed a nano-community to simultaneously restore the tumor vasculature and deliver the loaded drugs. Accordingly, improved drug delivery and therapeutic outcomes were achieved with no need to identify the precise time of the normalization window. Overall, our studies suggest that tumor vessel normalization therapy and nanomedicine design could be combined in one entity, using two waves of normalization strategies to achieve optimal chemo drug delivery into solid tumors.
机译：肿瘤血管标准化理论为合理使用抗血管生成剂和化学治疗剂开辟了门。然而，由于缺乏循环生物标志物和繁琐的剂量制度，努力抓住归一化窗口的努力在临床应用中产生了血管标准化治疗的发展。将欧洲剃须刀应用于治疗设计启发了我们构建有效和简单的肿瘤血管标准化促使战略。在此，我们开发了肿瘤血管标准化，提示由具有低分子量肝素（LMWH）和吉西他滨（GEM）制成的含有抗血管生成剂制成的纳米疫苗脂质衍生物缀合物（LGC）。这种治疗利用抗血管内皮生长因子（VEGF）治疗和度量化化疗（MET）的互补作用来增强肿瘤血管标准化效应。此外，通过将细胞毒性药物（例如紫杉醇（PTX）加载到LGC中，我们构建了一种纳米群落，同时恢复肿瘤脉管系统并递送负载的药物。因此，实现了改善的药物递送和治疗结果，无需确定归一化窗口的精确时间。总体而言，我们的研究表明，肿瘤血管标准化治疗和纳米医生设计可以在一个实体中组合，使用两波的正常化策略来实现最佳的化疗药物输送到实体瘤中。

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  • 来源
    《Biomaterials Science》 |2019年第3期|共14页
  • 作者

    Du Shi; Xiong Hui; Xu Cheng; Lu Yun; Yao Jing;

  • 作者单位

    China Pharmaceut Univ Dept Pharmaceut State Key Lab Nat Med 24 Tongjiaxiang Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Dept Pharmaceut State Key Lab Nat Med 24 Tongjiaxiang Nanjing 210009 Jiangsu Peoples R China;

    China Pharmaceut Univ Dept Pharmaceut State Key Lab Nat Med 24 Tongjiaxiang Nanjing 210009 Jiangsu Peoples R China;

    Jiangsu Hengrui Med Co Ltd Pharmaceut R&

    D Inst 7 Kunlunshan Rd Lianyungang 222047 Peoples R China;

    China Pharmaceut Univ Dept Pharmaceut State Key Lab Nat Med 24 Tongjiaxiang Nanjing 210009 Jiangsu Peoples R China;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子生物学;
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