title: Effectiveness of localized ultrasound-targeted microbubble destruction with doxorubicin liposomes in H22 mouse hepatocellular carcinoma model.
abstract: OBJECTIVE
  In order to increase local drug concentration and reduce systemic side effects of liver cancer chemotherapy, it is desirable to develop novel non-invasive technologies for drug targeting, such as ultrasound-targeted microbubble destruction (UTMD).
  
  
  METHODS
  H22 hepatocellular carcinoma (HCC) xenograft transplantation model was generated in UTMD study. BALB/c mice were randomly divided into six groups: doxorubicin HCl liposomal injection (DOX), DOX + US, UTMD, DOX + UTMD, H22 liver tumor control (CH control) and blank control group. The therapeutic schedule started on day 4 after tumor inoculation.
  
  
  RESULTS
  Average survival time of the animal model was approximately 18 d. The UTMD therapy parameters were optimized in the H22 mouse model to be: microbubble (MB) diameter, 2.30 ± 0.25 μm; MB density, 4.0 × 10(9) bubbles/ml; treatment dose, 0.2 ml per 20 g mouse body weight; sonication frequency, 1.3 MHz; and sonication power, 2.06 W/cm(2). Mice treated with DOX + UTMD had the smallest tumor volume and weight (p < 0.001), and the highest tumor inhibition rate (p < 0.01), intratumoral DOX concentration (p < 0.001) and survival rate among all tumor-burden groups (p < 0.001). Cell viability in different treatment groups was also assessed using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.
  
  
  CONCLUSIONS
  An improved antitumor effect was observed with the combination therapy of DOX and UTMD, as compared with treatment with DOX, DOX + US or UTMD, which implicates a novel approach for HCC treatment.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Chongqing Medical University , Chongqing , PR China and.
authors.forename: Fangyu
authors.initials: F
authors.lastname: Zhu
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.forename: Fang
authors.initials: F
authors.lastname: Luo
authors.forename: Pan
authors.initials: P
authors.lastname: Li
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D008113:Liver Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D045423:Microbubbles; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology; D015996:Survival Rate; D014463:Ultrasonography; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: Acoustic cavitation; HCC therapy; doxorubicin liposome; liver tumor; ultrasound-targeted microbubble destruction