title: Systemic Administration of siRNA via cRGD-containing Peptide.
abstract: Although small interfering RNAs (siRNAs) have been demonstrated to specifically silence their target genes in disease models and clinical trials, in vivo siRNA delivery is still the technical bottleneck that limits their use in therapeutic applications. In this study, a bifunctional peptide named RGD10-10R was designed and tested for its ability to deliver siRNA in vitro and in vivo. Because of their electrostatic interactions with polyarginine (10R), negatively charged siRNAs were readily complexed with RGD10-10R peptides, forming spherical RGD10-10R/siRNA nanoparticles. In addition to enhancing their serum stability by preventing RNase from attacking siRNA through steric hindrance, peptide binding facilitated siRNA transfection into MDA-MB-231 cells, as demonstrated by FACS and confocal microscopy assays and by the repressed expression of target genes. When RGD10 peptide, a receptor competitor of RGD10-10R, was added to the transfection system, the cellular internalization of RGD10-10R/siRNA was significantly compromised, suggesting a mechanism of ligand/receptor interaction. Tissue distribution assays indicated that the peptide/siRNA complex preferentially accumulated in the liver and in several exocrine/endocrine glands. Furthermore, tumor-targeted delivery of siRNA was also demonstrated by in vivo imaging and cryosection assays. In summary, RGD10-10R might constitute a novel siRNA delivery tool that could potentially be applied in tumor treatment.
authors: Institute of Molecular Medicine; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China.
authors: Yuanyu
authors: Y
authors: Huang
authors: Institute of Molecular Medicine; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China.
authors: Xiaoxia
authors: X
authors: Wang
authors: Institute of Molecular Medicine; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China.
authors: Weiyan
authors: W
authors: Huang
authors: Institute of Molecular Medicine; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China.
authors: Qiang
authors: Q
authors: Cheng
authors: Institute of Molecular Medicine; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China.
authors: Shuquan
authors: S
authors: Zheng
authors: Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China.
authors: Shutao
authors: S
authors: Guo
authors: Institute of Molecular Medicine; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China.
authors: Huiqing
authors: H
authors: Cao
authors: Chinese Academy of Sciences Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, National Center for Nanoscience and Technology of China, Beijing 100190, China.
authors: Xing-Jie
authors: XJ
authors: Liang
authors: Institute of Molecular Medicine; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China.
authors: Quan
authors: Q
authors: Du
authors: Institute of Molecular Medicine; State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China.|Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072, China.
authors: Zicai
authors: Z
authors: Liang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016923:Cell Death; D045744:Cell Line, Tumor; D024202:Electrophoretic Mobility Shift Assay; D004705:Endocytosis; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000737:chemistry / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage*; D012260:Ribonucleases / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D014018:Tissue Distribution
chemical_list: D010456:Peptides, Cyclic; D034741:RNA, Small Interfering; C507169:cyclic arginine-glycine-aspartic acid peptide; D012260:Ribonucleases