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首页> 外文期刊>Molecular pharmaceutics >Normalizing Tumor Vessels To Increase the Enzyme-Induced Retention and Targeting of Gold Nanoparticle for Breast Cancer Imaging and Treatment
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Normalizing Tumor Vessels To Increase the Enzyme-Induced Retention and Targeting of Gold Nanoparticle for Breast Cancer Imaging and Treatment

机译：正常化肿瘤血管以增加酶诱导的金纳米粒子靶向乳腺癌成像和治疗的保留和靶向

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摘要

Abnormal tumor vessels impede the transport and distribution of chemotherapeutics, resulting in low drug concentration at tumor sites and compromised drug efficacy. Normalizing tumor vessels can modulate tumor vascular permeability, alleviate tumor hypoxia, increase blood perfusion, attenuate interstitial fluid pressure, and improve drug delivery. Herein, a novel strategy combining cediranib, a tumor vessel normalizing agent, with an enzyme responsive size-changeable gold nanoparticle (AuNPs-A&C) was developed. In vivo photoacoustic and fluorescence imaging showed that oral pretreatment with 6 mg/kg/day of cediranib for two consecutive days significantly enhanced the retention of AuNPs-A&C in 4T1 tumor. In vivo photoacoustic imaging for hemoglobin (Hb) and oxyhemoglobin (HbO(2)), Evans blue assay, and immunofluorescence assay showed that cediranib pretreatment markedly increased tumor vascular permeability and tumor oxygenation, while distinctly decreased the tumor microvessel density, demonstrating normalized tumor vessels and favorably altered microenvironment. Additionally, the combination strategy considerably elevated the tumor targeting capacity of different nanoparticle formulations (AuNPs-PEG, AuNPs-A&C), while coadministration of cediranib and AuNPs-A&C achieved prevailing tumor targeting and antitumor efficacy in 4T1 tumor bearing mouse model. In conclusion, we report a novel combined administration strategy to further improve tumor diagnosis and treatment.
机译：肿瘤血管异常妨碍化学治疗剂的运输和分布，导致肿瘤部位的低药物浓度并受损药物功效。正常化肿瘤血管可以调节肿瘤血管渗透性，缓解肿瘤缺氧，增加血液灌注，衰减间质液压，并改善药物递送。在此，开发了一种新的策略，组合Cediranib，肿瘤血管标准化剂，具有酶反应性致敏尺寸可变的金纳米颗粒（AUNPS-A＆C）。体内光声和荧光成像表明，连续两天具有6mg / kg / kg / kg /天的口腔预处理显着增强了4T1肿瘤中AUNPS-A＆C的保留。在体内光声成像和氧合血红蛋白（HBO（2））中，evans蓝色测定和免疫荧光测定表明，Cediranib预处理显着增加了肿瘤血管渗透性和肿瘤氧合，同时明显降低了肿瘤微血管密度，展示了归一化肿瘤血管并且有利地改变了微环境。另外，组合策略显着升高了不同纳米颗粒制剂的肿瘤靶向能力（AUNPS-PEG，AUNPS-A＆C），而Cediranib和AuNPS-A＆C的共同分析在4T1肿瘤轴模型中实现了普遍的肿瘤靶向和抗肿瘤功效。总之，我们报告了一种新的组合给药策略，以进一步改善肿瘤诊断和治疗。

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  • 来源
    《Molecular pharmaceutics》 |2017年第10期|共10页
  • 作者

    Xiao Wei; Ruan Shaobo; Yu Wenqi; Wang Ranran; Hu Chuan; Liu Rui; Gao Huile;

  • 作者单位

    Sichuan Univ West China Sch Pharm Key Lab Drug Targeting &

    Drug Delivery Syst Chengdu 610041;

    Sichuan Univ West China Sch Pharm Key Lab Drug Targeting &

    Drug Delivery Syst Chengdu 610041;

    Sichuan Univ West China Sch Pharm Key Lab Drug Targeting &

    Drug Delivery Syst Chengdu 610041;

    Sichuan Univ West China Sch Pharm Key Lab Drug Targeting &

    Drug Delivery Syst Chengdu 610041;

    Sichuan Univ West China Sch Pharm Key Lab Drug Targeting &

    Drug Delivery Syst Chengdu 610041;

    Sichuan Univ West China Sch Pharm Key Lab Drug Targeting &

    Drug Delivery Syst Chengdu 610041;

    Sichuan Univ West China Sch Pharm Key Lab Drug Targeting &

    Drug Delivery Syst Chengdu 610041;

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

    cediranib; vessel normalization; 4T1 tumor; gold nanoparticles; drug delivery;

    机译：Cediranib;血管标准化;4T1肿瘤;金纳米颗粒;药物递送;

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