title: The inhibition of metastasis and growth of breast cancer by blocking the NF-κB signaling pathway using bioreducible PEI-based/p65 shRNA complex nanoparticles.
abstract: Metastasis is one of the greatest challenges in cancer treatment. In this study, a bioreducible polymer, Tween 85-s-s-polyethyleneimine 2K (TSP), was synthesized and used as a non-viral gene vector for p65 shRNA to block NF-κB signaling pathway, thereby inhibiting the growth and metastasis of breast cancer. The TSP/p65 shRNA complex nanoparticles (TSNs) could significantly down-regulate p65 expression in breast cancer cells due to the rapid degradation of TSP with prompt shRNA release, and consequently not only inhibit cell proliferation and invasion, but also induce cell apoptosis and disrupt the tube formation. Most importantly, TSNs showed high accumulation in tumor and almost completely inhibited the growth and metastasis of the breast cancer xenograft in nude mice induced by MDA-MB-435 cells. All these results indicated the promising of TSP as a non-viral gene vector to knock down p65 expression and inhibit the growth and metastasis of breast cancer.
authors.affiliation: Center of Pharmaceutics, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Jisheng
authors.initials: J
authors.lastname: Xiao
authors.forename: Xiaopin
authors.initials: X
authors.lastname: Duan
authors.forename: Qi
authors.initials: Q
authors.lastname: Yin
authors.forename: Zehong
authors.initials: Z
authors.lastname: Miao
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.forename: Chunying
authors.initials: C
authors.lastname: Chen
authors.forename: Zhiwen
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Yaping
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry; D001943:Breast Neoplasms / Q000098:blood supply / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D048430:Cell Shape; D019938:Cyclin D1 / Q000378:metabolism; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D009682:Magnetic Resonance Spectroscopy; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000473:pathology; D011094:Polyethyleneimine / Q000138:chemical synthesis / Q000737:chemistry*; D011136:Polysorbates; D034741:RNA, Small Interfering / Q000378:metabolism*; D015398:Signal Transduction; D014018:Tissue Distribution; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D001672:Biocompatible Materials; D011136:Polysorbates; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D019938:Cyclin D1; D011094:Polyethyleneimine; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9