title: ZEB1 knockdown mediated using polypeptide cationic micelles inhibits metastasis and effects sensitization to a chemotherapeutic drug for cancer therapy.
abstract: Metastasis and drug resistance are the main causes for the failure in clinical cancer therapy. Emerging evidence suggests an intricate role of epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs) in metastasis and drug resistance. The EMT-activator ZEB1 is crucial in malignant tumor progression by linking EMT-activation and stemness-maintenance. Here, we used multifunctional polypeptide micelle nanoparticles (NP) as nanocarriers for the delivery of ZEB1 siRNA and doxorubicin (DOX). The nanocarriers could effectively deliver siRNA to the cytoplasm and knockdown the target gene in H460 cells and H460 xenograft tumors, leading to reduced EMT and repressed CSC properties in vitro and in vivo. The complex micelle nanoparticles with ZEB1 siRNA (siRNA-NP) significantly reduced metastasis in the lung. When DOX and siRNA were co-delivered by the nanocarriers (siRNA-DOX-NP), a synergistic therapeutic effect was observed, resulting in dramatic inhibition of tumor growth in a H460 xenograft model. These results demonstrated that the siRNA-NP or siRNA-DOX-NP complex targeting ZEB1 could be developed into a new therapeutic approach for non-small cell lung cancer (NSCLC) treatment.
authors.affiliation: Guangdong Key Laboratory of Nanomedicine, Shenzhen Key Laboratory of Cancer Nanotechnology, Institute of Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, Guangdong, P. R. China. lt.cai@siat.ac.cn.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Fang
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.forename: Mingxing
authors.initials: M
authors.lastname: Li
authors.forename: Huqiang
authors.initials: H
authors.lastname: Yi
authors.forename: Guanhui
authors.initials: G
authors.lastname: Gao
authors.forename: Zonghai
authors.initials: Z
authors.lastname: Sheng
authors.forename: Ping
authors.initials: P
authors.lastname: Gong
authors.forename: Yifan
authors.initials: Y
authors.lastname: Ma
authors.forename: Lintao
authors.initials: L
authors.lastname: Cai
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D002412:Cations; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000008:administration & dosage* / Q000737:chemistry; D004357:Drug Synergism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics*; D020868:Gene Silencing; D015316:Genetic Therapy / Q000379:methods; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008422:Materials Testing; D008823:Micelles; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D009362:Neoplasm Metastasis / Q000235:genetics / Q000517:prevention & control*; D010455:Peptides / Q000737:chemistry; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D002412:Cations; D018398:Homeodomain Proteins; D008823:Micelles; D053769:Nanocapsules; D010455:Peptides; D034741:RNA, Small Interfering; D014157:Transcription Factors; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1; D004317:Doxorubicin