title: CD44 antibody-targeted liposomal nanoparticles for molecular imaging and therapy of hepatocellular carcinoma.
abstract: Most hepatocellular carcinoma (HCC) therapies fail to target cancer stem cells (CSCs) and monitor cancer progression or regression. The purpose of this study was to evaluate the possibility of cancer imaging and simultaneously monitoring targeted therapy in a single animal by anti-CD44 antibody-mediated liposomal nanoparticle. In this study, an in situ liver tumor model was applied for therapy by injecting 1.0 × 10(6) HepG2 cells carrying a reporter system encoding a double fusion (DF) reporter gene consisting of firefly luciferase (Fluc) and green fluorescent protein (GFP) into the liver of NOD/SCID mice. A strategy was developed which specifically targeted HCC via anti-CD44 antibody-mediated liposomal nanoparticle delivery, loaded of either doxorubicin (Dox) or a triple fusion (TF) gene containing the herpes simplex virus truncated thymidine kinase (HSV-ttk) and renilla luciferase (Rluc) and red fluorescent protein (RFP). The NOD/SCID mice were subsequently treated with ganciclovir (GCV) and the growth status of tumor was monitored by optical bioluminescence imaging (BLI) of Fluc and specific targeting of the liposomal nanoparticle was tracked by Rluc imaging. CD44 antibody-mediated liposomal nanoparticle, loaded of TF plasmids, were shown to be useful for monitoring and evaluating targeting efficacy and gene therapy by non-invasive molecular imaging. Here, we demonstrate the time intensive preclinical steps involved in molecular target identification, validation, and characterization by dual molecular imaging. This targeted and traceable therapeutic strategy has potential advantages to overcome the problems of conventional tumor therapy and may open a new application for the treatment of HCC by targeting CSCs.
authors.affiliation: Department of Immunology, Nankai University School of Medicine, Tianjin 300071, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.forename: Weijun
authors.initials: W
authors.lastname: Su
authors.forename: Ze
authors.initials: Z
authors.lastname: Liu
authors.forename: Manqian
authors.initials: M
authors.lastname: Zhou
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.forename: Yanan
authors.initials: Y
authors.lastname: Chen
authors.forename: Dan
authors.initials: D
authors.lastname: Lu
authors.forename: Yanhua
authors.initials: Y
authors.lastname: Liu
authors.forename: Yan
authors.initials: Y
authors.lastname: Fan
authors.forename: Yizhou
authors.initials: Y
authors.lastname: Zheng
authors.forename: Zhongchao
authors.initials: Z
authors.lastname: Han
authors.forename: Deling
authors.initials: D
authors.lastname: Kong
authors.forename: Joseph C
authors.initials: JC
authors.lastname: Wu
authors.forename: Rong
authors.initials: R
authors.lastname: Xiang
authors.forename: Zongjin
authors.initials: Z
authors.lastname: Li
mesh_terms: D000818:Animals; D000906:Antibodies / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000473:pathology* / Q000628:therapy*; D049452:Green Fluorescent Proteins / Q000235:genetics; D018960:Hyaluronan Receptors / Q000276:immunology*; D008081:Liposomes; D008113:Liver Neoplasms / Q000473:pathology* / Q000628:therapy*; D008156:Luciferases / Q000235:genetics; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D057054:Molecular Imaging; D053758:Nanoparticles
chemical_list: D000906:Antibodies; D018960:Hyaluronan Receptors; D008081:Liposomes; D049452:Green Fluorescent Proteins; D008156:Luciferases