A novel cell-penetrating peptide TAT-A1 delivers siRNA into tumor cells selectively |
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Authors: | Bing Fang Lu Jiang Ming Zhang Fa Zheng Ren |
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Affiliation: | 1. Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, P.O. Box 287, No. 17 Qinghua East Road, Haidian, Beijing 100083, China;2. Beijing Higher Institution Engineering Research Center of Animal Product, China Agricultural University, Beijing 100083, China;3. Beijing Key Laboratory of Nutrition, Health & Food Safety, China Agricultural University, Beijing 100083, China |
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Abstract: | siRNA is promising in anti-tumor therapy. The main challenge is lack of tumor-specific intracellular delivery. In this study, a 6 amino acids peptide (A1) with high affinity for vascular endothelial growth factor receptor-1 (VEGFR1) was conjugated with a cell penetrating peptide (CPP) TAT to form a tumor-selective CPP. To evaluate the tumor-targeted penetrate property of TAT-A1, the uptake of TAT-A1 was measured by flow cytometry. The selectivity in vitro was tested in co-cultured tumor cells and normal cells by laser confocal microscope. The internalization efficiency of TAT-A1 was significantly higher than that of TAT (p < 0.05). TAT-A1 penetrated into tumor cells selectively when added to co-cultured tumor cells and normal cells due to the recognition of VEGFR1 which is over-expressed on tumor cells. Furthermore, siRNA was successfully transferred by TAT-A1 into tumor cells in a similar way of Lipofectamine 2000, which was proved to be an efficient vector. The knockout effect of siRNA transferred by TAT-A1 was obtained at both mRNA and protein level. These results indicated that the tumor-targeted TAT-A1 can act as an excellent vehicle for specific delivery of anti-cancer agents. |
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Keywords: | Tumor-targeting Cell penetrating peptide A1 siRNA Vascular endothelial growth factor receptor-1 |
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