title: Nanoparticle siRNA against BMI-1 with a Polyethylenimine-Laminarin Conjugate for Gene Therapy in Human Breast Cancer.
abstract: The B-cell-specific Moloney leukemia virus inset site 1 gene (BMI-1) has attracted considerable attention in recent years because of its key role in breast cancer development and metastasis. The downregulation of BMI-1 expression via small interfering RNA (siRNA) effectively inhibits tumor growth. However, the successful application of this therapy is limited by the unavailability of an appropriate vector for siRNA transfer. Therefore, this study aimed to construct a novel laminarin-based nonviral gene transfer vector to carry a constructed BMI-1-targeting siRNA and to investigate the in vitro and in vivo antitumor effects of this siRNA on breast cancer cells. To enhance the siRNA-carrying capacity, we introduced polyethylenimine (PEI) to laminarin's surface via N,N'-carbonyldiimidazole, which produced the cationic PEI-modified laminarin conjugate nLP. Subsequent in vitro experiments indicated that nLP not only formed a nanoparticle with a diameter of 200 nm through electrostatic interactions with siRNA but also showed high efficiency (95.0%) in the delivery siRNA to MCF-7 cells. The nanoparticle targeting BMI-1 (nLP/siBMI-2) reduced BMI-1 expression in breast MCF-7 cells by 90.9% reduction. An in vivo tumor suppression experiment demonstrated that the nLP/siBMI-2 nanoparticle had relatively low toxicity and good gene-therapeutic efficacy, with a tumor inhibition rate of 46.6%.
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University , 100 Kexue Avenue, Zhengzhou 450001, China.
authors.forename: Xueling
authors.initials: X
authors.lastname: Ren
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Zhengzhou University , Zhengzhou 450052, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University , 100 Kexue Avenue, Zhengzhou 450001, China.
authors.forename: Yuxue
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University , 100 Kexue Avenue, Zhengzhou 450001, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University , 100 Kexue Avenue, Zhengzhou 450001, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Zhengzhou University , 100 Kexue Avenue, Zhengzhou 450001, China.
authors.forename: Zhenzhong
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Pathology, The First Affiliated Hospital of Zhengzhou University , Zhengzhou 450052, China.|Department of Pathology, Basic Medical College of Zhengzhou University , 100 Kexue Avenue, Zhengzhou 450001, China.
authors.forename: Huixiang
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000628:therapy*; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005936:Glucans / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D008807:Mice, Inbred BALB C; D048054:Mitogen-Activated Protein Kinase 7 / Q000235:genetics*; D058990:Molecular Targeted Therapy; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000633:toxicity; D011094:Polyethyleneimine / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D005936:Glucans; D034741:RNA, Small Interfering; D011094:Polyethyleneimine; C008247:laminaran; C481581:MAPK7 protein, human; D048054:Mitogen-Activated Protein Kinase 7