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Enhanced Nanodrug Delivery to Solid Tumors Based on a Tumor Vasculature-Targeted Strategy

机译：基于肿瘤血管靶向策略的增强纳米药物向实体肿瘤的递送。

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Tumor angiogenesis is a hallmark of tumor growth and metastasis, and inhibition of tumor angiogenesis is an effective strategy for tumor therapy. The high expression levels of specific biomarkers such as integrin receptors (e.g., alpha(v)/beta(3)) in the endothelium of tumor vessels make angiogenesis an ideal target for drug delivery and thus tumor therapy. Herein, a new nanodrug (T&D@RGD-Ag2S) is presented, which can effectively inhibit tumor growth by integrating the specific recognition peptide cyclo(Arg-Gly-Asp-d-Phe-Cys) (cRGD) for tumor vascular targeting, the broad-spectrum endothelial inhibitor O-(chloroacetyl-carbamoyl) fumagillol (TNP-470), and chemotherapeutic drug doxorubicin (DOX) for synergetic tumor therapy. The results show that the T&D@RGD-Ag2S nanodrug rapidly and specifically binds to the tumor vasculature after intravenous injection. Tumor vascular density is greatly reduced following effective angiogenesis inhibition by TNP-470. Meanwhile, increased delivery of DOX deep into the tumor induces extensive tumor apoptosis, resulting in remarkable tumor growth inhibition in a human U87-MG malignant glioma xenograft model. In addition, the therapeutic effects of T&D@RGD-Ag2S on inhibiting tumor growth and decreasing vessel density are monitored in situ using near-infrared II (NIR-II) fluorescence imaging of Ag2S quantum dots. This tumor vasculature-targeted strategy can be extended as a general method for treating a broad range of tumors and holds promise for future clinical applications.
机译：肿瘤血管生成是肿瘤生长和转移的标志，而抑制肿瘤血管生成是肿瘤治疗的有效策略。特定生物标志物例如整联蛋白受体（例如，α（v）/ beta（3））在肿瘤血管内皮中的高表达水平使血管生成成为药物输送和肿瘤治疗的理想靶标。在这里，提出了一种新的纳米药物（T＆D @ RGD-Ag2S），它可以通过整合用于肿瘤血管靶向的特异性识别肽环（Arg-Gly-Asp-d-Phe-Cys）（cRGD）来有效抑制肿瘤的生长。广谱内皮抑制剂O-（氯乙酰氨基甲酰基）烟曲霉醇（TNP-470）和化疗药物阿霉素（DOX）用于协同肿瘤治疗。结果表明，T＆D @ RGD-Ag2S纳米药物在静脉注射后迅速且特异性地与肿瘤脉管系统结合。 TNP-470有效抑制血管生成后，肿瘤血管密度大大降低。同时，在人类U87-MG恶性神经胶质瘤异种移植模型中，增加DOX深入肿瘤的传递会诱导广泛的肿瘤凋亡，从而导致显着的肿瘤生长抑制。此外，使用Ag2S量子点的近红外II（NIR-II）荧光成像原位监测T＆D @ RGD-Ag2S对抑制肿瘤生长和降低血管密度的治疗效果。这种靶向肿瘤脉管系统的策略可以扩展为治疗多种肿瘤的通用方法，并有望在未来的临床应用中发挥作用。

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  • 来源
    《Advanced Functional Materials》 |2016年第23期|4192-4200|共9页
  • 作者

    Song Chenghua; Zhang Yejun; Li Chunyan; Chen Guangcun; Kang Xiaofeng; Wang Qiangbin;

  • 作者单位

    Northwest Univ, Coll Chem & Mat Sci, Minist Educ, Key Lab Synthet & Nat Funct Mol Chem, Xian 710069, Peoples R China|Chinese Acad Sci, Suzhou Inst Nanotech & Nanobion, Div Nanobiomed, Key Lab Nanobio Interface, Suzhou 215123, Peoples R China|Chinese Acad Sci, Suzhou Inst Nanotech & Nanobion, I Lab, Suzhou 215123, Peoples R China;

    Chinese Acad Sci, Suzhou Inst Nanotech & Nanobion, Div Nanobiomed, Key Lab Nanobio Interface, Suzhou 215123, Peoples R China|Chinese Acad Sci, Suzhou Inst Nanotech & Nanobion, I Lab, Suzhou 215123, Peoples R China;

    Chinese Acad Sci, Suzhou Inst Nanotech & Nanobion, Div Nanobiomed, Key Lab Nanobio Interface, Suzhou 215123, Peoples R China|Chinese Acad Sci, Suzhou Inst Nanotech & Nanobion, I Lab, Suzhou 215123, Peoples R China;

    Chinese Acad Sci, Suzhou Inst Nanotech & Nanobion, Div Nanobiomed, Key Lab Nanobio Interface, Suzhou 215123, Peoples R China|Chinese Acad Sci, Suzhou Inst Nanotech & Nanobion, I Lab, Suzhou 215123, Peoples R China;

    Northwest Univ, Coll Chem & Mat Sci, Minist Educ, Key Lab Synthet & Nat Funct Mol Chem, Xian 710069, Peoples R China;

    Chinese Acad Sci, Suzhou Inst Nanotech & Nanobion, Div Nanobiomed, Key Lab Nanobio Interface, Suzhou 215123, Peoples R China|Chinese Acad Sci, Suzhou Inst Nanotech & Nanobion, I Lab, Suzhou 215123, Peoples R China;

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