title: Cationic microRNA-delivering nanovectors with bifunctional peptides for efficient treatment of PANC-1 xenograft model.
abstract: Therapeutic strategies based on modulation of microRNA activity possess much promise in cancer therapy, but the in vivo delivery of microRNA to target sites and its penetration into tumor tissues remain great challenge. In this work, miR-34a-delivering therapeutic nanocomplexes with a tumor-targeting and -penetrating bifunctional CC9 peptide were proposed for efficient treatment of pancreatic cancers. In vitro study indicated that the nanoparticle-based miR-34a delivery systems could effectively facilitate cellular uptake and greatly up-regulate the mRNA level of miR-34a in PANC-1 cell lines. The up-regulation of miR-34a remarkably induced cell cycle arrest and apoptosis, suppressed the tumor cell migration and inhibited the target gene expressions such as E2F3, Bcl-2, c-myc and cyclin D1. More importantly, the in vivo systemic administration of the developed targeting miR-34a delivery systems in a pancreatic cancer model significantly inhibited tumor growth and induced cancer cell apoptosis. Such bifunctional peptide-conjugated miRNA-delivering nanocomplexes should have great potential applications in cancer therapy.
authors.affiliation: Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou, 310028, China.
authors.forename: Q L
authors.initials: QL
authors.lastname: Hu
authors.forename: Q Y
authors.initials: QY
authors.lastname: Jiang
authors.forename: X
authors.initials: X
authors.lastname: Jin
authors.forename: J
authors.initials: J
authors.lastname: Shen
authors.forename: K
authors.initials: K
authors.lastname: Wang
authors.forename: Y B
authors.initials: YB
authors.lastname: Li
authors.forename: F J
authors.initials: FJ
authors.lastname: Xu
authors.forename: G P
authors.initials: GP
authors.lastname: Tang
authors.forename: Z H
authors.initials: ZH
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050699:E2F3 Transcription Factor / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D053758:Nanoparticles / Q000737:chemistry; D036103:Nanotechnology / Q000379:methods*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010455:Peptides / Q000737:chemistry*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D023041:Xenograft Model Antitumor Assays; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; C530104:CCND1 protein, human; D050699:E2F3 Transcription Factor; C098319:E2F3 protein, human; C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D010455:Peptides; D016271:Proto-Oncogene Proteins c-myc; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1