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

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• 作者：Chenghua Song ; Yejun Zhang ; Chunyan Li ; Guangcun Chen ; Xiaofeng Kang and Qiangbin Wang
• 刊名：Advanced Functional Materials
• 出版年：2016
• 出版时间：June 20, 2016
• 年：2016
• 卷：26
• 期：23
• 页码：4192-4200
• 全文大小：2929K
• ISSN：1616-3028

文摘

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., α_vβ₃) 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.