title: Low-intensity focused ultrasound mediated localized drug delivery for liver tumors in rabbits.
abstract: OBJECTIVE
  To explore the antitumor effects of low-intensity focused ultrasound (LIFU) mediated localized drug delivery of adriamycin-microbubble-PLGA nanoparticle complexes on rabbits VX2 liver tumor.
  
  
  METHODS
  ADM-NMCs were prepared by covalent linking of ADM-PLGA nanoparticles (ADM-NPs) to the shell of the microbubbles. A fixed water bag filled with microbubbles was subjected to LIFU and non-focused ultrasound respectively, and the ultrasound images of which were recorded before and after ultrasonication. A total of 54 VX2 liver tumor-burdened rabbits were divided into six groups randomly, including control, ADM-NPs combined with LIFU, microbubbles combined with LIFU, ADM-NPs and microbubbles combined with LIFU, ADM-NMCs combined with LIFU and ADM-NMCs combined with Non-FUS. The tumor volume and volume inhibition rate (VIR) of tumor progression were calculated and compared. Apoptotic cells were labeled by terminal deoxyuridine nick end. Proliferating cell nuclear antigen was detected by immunohistochemistry. The median survival time of the animals were recorded and compared.
  
  
  RESULTS
  ADM-NMCs were successfully prepared with an average diameter of 1721 nm. The highest VIR and apoptotic index (AI) were found in the group of ADM-NMCs combined with LIFU while the lowest proliferating index (PI) was simultaneously observed in this group. The median survival time of the rabbits in the ADM-NMCs combined with LIFU group was the longest (71days) among all groups.
  
  
  CONCLUSIONS
  ADM-NMCs combined with LIFU could inhibit the rabbits VX2 liver tumor progress by delaying the tumor proliferation and accelerating apoptosis, which presents a novel process for liver tumor targeting chemotherapy.
authors.affiliation: a Second Affiliated Hospital , Chongqing Medical University , Chongqing , P. R. China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Gong
authors.affiliation: a Second Affiliated Hospital , Chongqing Medical University , Chongqing , P. R. China.|b Institute of Ultrasound Imaging , Chongqing Medical University , Chongqing , P. R. China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a Second Affiliated Hospital , Chongqing Medical University , Chongqing , P. R. China.
authors.forename: Guifang
authors.initials: G
authors.lastname: Dong
authors.affiliation: a Second Affiliated Hospital , Chongqing Medical University , Chongqing , P. R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.affiliation: a Second Affiliated Hospital , Chongqing Medical University , Chongqing , P. R. China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: a Second Affiliated Hospital , Chongqing Medical University , Chongqing , P. R. China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Rong
authors.affiliation: c First Affiliated Hospital , Chongqing Medical University , Chongqing , P. R. China , and.
authors.forename: Maoping
authors.initials: M
authors.lastname: Li
authors.affiliation: d Children's Hospital of Chongqing Medical University , Chongqing , P. R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: a Second Affiliated Hospital , Chongqing Medical University , Chongqing , P. R. China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Ran
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems / Q000379:methods*; D019344:Lactic Acid / Q000737:chemistry; D008099:Liver / Q000187:drug effects*; D008113:Liver Neoplasms / Q000188:drug therapy*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy*; D045423:Microbubbles; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011817:Rabbits; D047368:Tumor Burden / Q000187:drug effects; D014465:Ultrasonics / Q000379:methods; D014463:Ultrasonography / Q000379:methods
chemical_list: D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin
keywords: ADM-NMCs; LIFU; PLGA nanoparticles; VX2 Liver cancer; microbubble