Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 26, Issue 23, Pages 4192-4200Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201600417
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Funding
- Chinese Academy of Sciences Strategic Priority Research Program [XDA01030200]
- National Natural Science Foundation of China [21303249, 21425103, 81401464, 21501192]
- Natural Science Foundation of Jiangsu Province [BK20130366]
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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.
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