title: A novel cell-penetrating peptide TAT-A1 delivers siRNA into tumor cells selectively.
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.
authors.affiliation: Key Laboratory of Functional Dairy, College of Food Science and Nutritional Engineering, China Agricultural University, PO Box 287, No. 17 Qinghua East Road, Haidian, Beijing 100083, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Fang
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Fa Zheng
authors.initials: FZ
authors.lastname: Ren
mesh_terms: D001692:Biological Transport; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D015870:Gene Expression; D015696:Gene Products, tat / Q000138:chemical synthesis / Q000737:chemistry*; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000037:antagonists & inhibitors / Q000235:genetics; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry; D058990:Molecular Targeted Therapy; D009928:Organ Specificity; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry*; D012333:RNA, Messenger / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D015696:Gene Products, tat; D008055:Lipids; C086724:Lipofectamine; D010446:Peptide Fragments; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D040281:Vascular Endothelial Growth Factor Receptor-1