title: A redox-sensitive, oligopeptide-guided, self-assembling, and efficiency-enhanced (ROSE) system for functional delivery of microRNA therapeutics for treatment of hepatocellular carcinoma.
abstract: Lack of efficient adjuvant therapy contributes to a high incidence of recurrence and metastasis of hepatocellular carcinoma (HCC). A novel therapeutic is required for adjuvant treatment of HCC. We developed a polymer-based nanosystem (ROSE) for functional gene therapy by synthesizing a supramolecular complex self-assembled from polycations and functional adamantyl modules. The ROSE system condensing tumor suppressor microRNA-34a (miR-34a) therapeutics becomes ROSE/miR-34a nanoparticles that could facilitate gene transfection in HCC cells with satisfied stability and efficiency, possibly due to proton sponge effect by polycations, PEGlyation protection, and controlled release by breakdown of disulfide bonds. Meanwhile, modification with a targeting oligopeptide SP94 in ROSE/miR-34a enables approximately higher affinity for LM3 HCC cells than hepatocytes in vitro and greater HCC specificity in vivo. Furthermore, ROSE/miR-34a nanoparticles significantly inhibits HCC cell proliferation and in vivo tumor growth, representing a notable effect improvement over conventional gene delivery strategies. ROSE/miR-34a, featuring redox-responsiveness, oligopeptide-guided specificity, self-assembly, and enhanced transfection, is therefore a potential therapeutic agent in future adjuvant therapy for HCC treatment.
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China; Institute of Chemistry Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China.
authors.forename: Qida
authors.initials: Q
authors.lastname: Hu
authors.affiliation: Institute of Chemistry Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Huzhou Central Hospital, Huzhou 313000, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Sun
authors.affiliation: Institute of Chemistry Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China.
authors.forename: Qihan
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Hepatobiliary and Pancreatic Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China. Electronic address: liangtingbo@zju.edu.cn.
authors.forename: Tingbo
authors.initials: T
authors.lastname: Liang
authors.affiliation: Institute of Chemistry Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou 310028, China. Electronic address: tangguping@zju.edu.cn.
authors.forename: Guping
authors.initials: G
authors.lastname: Tang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000628:therapy*; D045744:Cell Line, Tumor; D003460:Crystallization / Q000379:methods; D004357:Drug Synergism; D015316:Genetic Therapy / Q000379:methods*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics / Q000627:therapeutic use*; D053769:Nanocapsules / Q000737:chemistry* / Q000648:ultrastructure; D009842:Oligopeptides / Q000737:chemistry / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction; D016896:Treatment Outcome
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs; D053769:Nanocapsules; D009842:Oligopeptides
keywords: Delivery system; Hepatocellular carcinoma; Multifunctional delivery; miRNA therapy