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首页> 外文期刊>Advanced Functional Materials >Nanoparticles Surmounting Blood-Brain Tumor Barrier Through Both Transcellular and Paracellular Pathways to Target Brain Metastases
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Nanoparticles Surmounting Blood-Brain Tumor Barrier Through Both Transcellular and Paracellular Pathways to Target Brain Metastases

机译：通过跨细胞和旁细胞途径靶向脑转移的纳米粒子超越血脑肿瘤屏障。

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摘要

Brain metastases are one of the most difficult malignancies to treat owing to their location and mostly multifocal and infiltrative growth. Chemotherapy, which is often effective against tumors outside the brain, offers some hope for brain metastases. However, the efficacy of systemic drug delivery to brain metastases is extremely limited due largely to the blood-brain tumor barrier (BTB). Herein, it is reported that minoxidil-loaded hyaluronic acid-tethered nanoparticles (M@H-NPs) can efficiently and specially surmount the BTB through both transcellular and paracellular pathways and target brain metastases through coordination of hyaluronic acid with CD44 target. The transcellular endocytosis, paracellular claudin-5 expression, and BTB crossing are evaluated to confirm that the developed M@H-NPs can be endued with minoxidil's ability to boost transcytosis and downregulate tight junction protein in BTB endothelial cells at brain metastases for promoted BTB penetration. M@H-NPs selectively deliver doxorubicin (DOX) to brain metastatic lesions, while sparing normal brain cells from harm. Treatment with M@H-NPs/DOX significantly prolongs median survival of mice bearing brain metastases. Due to the fruitful BTB penetration and brain metastasis homing, and improved therapeutic outcome, the minoxidil-based systemic drug delivery strategy may serve as a potential approach for clinical management of brain metastases.
机译：脑转移瘤由于其位置以及多灶性和浸润性生长而成为最难治疗的恶性肿瘤之一。化学疗法通常对脑外肿瘤有效，为脑转移提供了希望。然而，由于血脑肿瘤屏障（BTB），全身性药物递送至脑转移的功效极其有限。在此，据报道，负载有米诺地尔的透明质酸束缚的纳米颗粒（M @ H-NPs）可以通过跨细胞和旁细胞途径有效地和特别地超越BTB，并通过透明质酸与CD44靶点的协调作用靶向脑转移。对跨细胞内吞作用，旁细胞claudin-5表达和BTB交叉进行了评估，以证实所开发的M @ H-NPs可以被米诺地尔增强在脑转移时BTB内皮细胞中的转移能力和下调紧密连接蛋白的能力，以促进BTB渗透。 M @ H-NPs将阿霉素（DOX）选择性地递送至脑转移性病变，同时保护正常脑细胞免受伤害。用M @ H-NPs / DOX处理可显着延长患有脑转移的小鼠的中位生存期。由于卓有成效的BTB渗透和脑转移归巢，以及改善的治疗结果，基于米诺地尔的全身药物递送策略可能成为脑转移临床管理的潜在方法。

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  • 来源
    《Advanced Functional Materials》 |2019年第27期|1900259.1-1900259.15|共15页
  • 作者

    Miao Tongtong; Ju Xiufeng; Zhu Qiuning; Wang Yamei; Guo Qian; Sun Tao; Lu Chunzhu; Han Liang;

  • 作者单位

    Soochow Univ, Jiangsu Key Lab Neuropsychiat Dis Res, Suzhou 215123, Peoples R China|Soochow Univ, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China;

    Soochow Univ, Jiangsu Key Lab Neuropsychiat Dis Res, Suzhou 215123, Peoples R China|Soochow Univ, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China;

    Soochow Univ, Jiangsu Key Lab Neuropsychiat Dis Res, Suzhou 215123, Peoples R China|Soochow Univ, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China;

    Soochow Univ, Jiangsu Key Lab Neuropsychiat Dis Res, Suzhou 215123, Peoples R China|Soochow Univ, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China;

    Soochow Univ, Jiangsu Key Lab Neuropsychiat Dis Res, Suzhou 215123, Peoples R China|Soochow Univ, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China;

    Fudan Univ, Sch Pharm, Dept Pharmaceut, Minist Educ,Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China;

    ZhongKe Quantz Med Suzhou Co LTD, 407 Room,15 Bldg,8 Jinfeng Rd, Suzhou 215100, Peoples R China;

    Soochow Univ, Jiangsu Key Lab Neuropsychiat Dis Res, Suzhou 215123, Peoples R China|Soochow Univ, Coll Pharmaceut Sci, Suzhou 215123, Peoples R China;

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  • 正文语种 eng
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  • 关键词

    ATP-sensitive potassium channels; blood-brain tumor barrier; brain metastases; minoxidil sulfate; nanoparticles;

    机译：ATP敏感性钾通道;血脑肿瘤屏障;脑转移;硫酸米诺地尔;纳米颗粒;

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