title: Antitumoural hydroxyapatite nanoparticles-mediated hepatoma-targeted trans-arterial embolization gene therapy: in vitro and in vivo studies.
abstract: OBJECTIVE
  Absence of curative treatment creates urgent need for new strategies for unresectable hepatoma. Based on former discoveries of good liver cell compatibility, safety and tumour-specific inhibition of hydroxyapatite nanoparticles (nHAP), this work tries to make nHAP serve as gene vector in the hepatoma-targeted trans-arterial embolization (TAE) gene therapy to elevate and synergize the therapeutic efficacy of TAE and target gene therapy.
  
  
  METHODS
  Following dosage and ratio optimization, polypolex formed by surface modified nHAP and p53 expressing plasmid was applied in vitro for human hepatoma HePG2 cell, and then in vivo for rabbit hepatic VX2 tumour by injection of polypolex/lipodoil emulsion to the hepatic artery in a tumour-target manner.
  
  
  RESULTS
  In vitro, the polypolex transfected only about 5% HepG2 cells, but can elevate the inhibition of its growth and apoptosis in a much more degree while keeping safe to the normal hepatocyte line, L02. In vivo, the emulsion, with better dispersion than the polypolex and more specific tumour-target than lipiodol, mediated specific 4% p53 expression and antitumoural nanoparticle retention in the target tumour site, also significantly reduced tumour growth and prolonged the animal survival times more than the lipiodol (P < 0.05).
  
  
  CONCLUSIONS
  In all, this new treatment based on nHAP can enhance therapeutic effect of HCC safely both in vitro and in vivo.
authors.affiliation: Department of Ultrasound, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, Guangdong Province, China.
authors.forename: Gaopeng
authors.initials: G
authors.lastname: Li
authors.forename: Lu
authors.initials: L
authors.lastname: Ye
authors.forename: Jingsheng
authors.initials: J
authors.lastname: Pan
authors.forename: Miaoyun
authors.initials: M
authors.lastname: Long
authors.forename: Zizhuo
authors.initials: Z
authors.lastname: Zhao
authors.forename: Haiyun
authors.initials: H
authors.lastname: Yang
authors.forename: Jing
authors.initials: J
authors.lastname: Tian
authors.forename: Yanling
authors.initials: Y
authors.lastname: Wen
authors.forename: Shengli
authors.initials: S
authors.lastname: Dong
authors.forename: Jian
authors.initials: J
authors.lastname: Guan
authors.forename: Baoming
authors.initials: B
authors.lastname: Luo
mesh_terms: D000818:Animals; D017209:Apoptosis; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation; D017886:Durapatite / Q000008:administration & dosage*; D004621:Embolization, Therapeutic; D004998:Ethiodized Oil / Q000008:administration & dosage; D005240:Feasibility Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D056945:Hep G2 Cells; D006801:Humans; D007269:Injections, Intra-Arterial; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D008297:Male; D053758:Nanoparticles; D009336:Necrosis; D011817:Rabbits; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D004998:Ethiodized Oil; D017886:Durapatite