Synthesis and Antitumor Application of Antiangiogenetic Gold Nanoclusters
2021
Li, Qirong | Zhou, Ronghui | Sun, Yue | Xiao, Dexuan | Liu, Mengting | Zhao, Dan | Peng, Shuanglin | Chen, Yu | Lin, Yunfeng
Conventional antiangiogenetic inhibitors suffered from poor delivery problems that result in unsatisfactory antitumor treatment efficacy. Although the liposomes or nanomaterial-based delivery systems can improve the therapeutic efficacy of antiangiogenic molecules, the assembly process is far too complex. Herein, a nanomaterial or a new nanodrug that could work without the help of a carrier and could be easily synthesized is needed. Au nanoclusters (AuNCs) are a kind of ideal nanostructures that could spontaneously enter into the cell and could be synthesized by a relatively easy one-pot method. Here, changing the traditional ligand glutathione (GSH) into an anti-Flt1 peptide (AF) has enriched the newly synthesized AF@AuNCs with targeted antiangiogenic properties. Based on the specific binding between AF and vascular endothelial growth factor receptor 1 (VEGFR1), the interaction between VEGFR1 and its ligands could be blocked. Furthermore, the expression of VEGFR2 could be downregulated. Compared with pure AF peptide- and GSH-participated AuNCs (GSH@AuNCs), AF@AuNCs were more effective in inhibiting both tube formation and migration of the endothelial cells in vitro. Furthermore, the in vivo chick embryo chorioallantoic membrane (CAM) experiment and antitumor experiment were conducted to further verify the enhanced antiangiogenesis and tumor inhibition effect of AF@AuNCs. Our findings provide promising evidence of a carrier-free nanodrug for tumors and other vascular hyperproliferative diseases.
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