title: Ultrasound-mediated destruction of LHRHa-targeted and paclitaxel-loaded lipid microbubbles induces proliferation inhibition and apoptosis in ovarian cancer cells.
abstract: Although paclitaxel (PTX) is used with platinum as the first line chemotherapy regimen for ovarian cancer, its clinical efficacy is often limited by severe adverse effects. Ultrasound-targeted microbubble destruction (UTMD) technique holds a great promise in minimizing the side effects and maximizing the therapeutic efficacy. However, the technique typically uses nontargeted microbubbles with suboptimal efficiency. We synthesized targeted and PTX-loaded microbubbles (MBs) for UTMD mediated chemotherapy in ovarian cancer cells. PTX-loaded lipid MBs were coated with a luteinizing hormone-releasing hormone analogue (LHRHa) through a biotin-avidin linkage to target the ovarian cancer A2780/DDP cells that express the LHRH receptor. In the cell culture studies, PTX-loaded and LHRHa-targeted MBs (TPLMBs) in combination with ultrasound (300 kHz, 0.5 W/cm(2), 30 s) demonstrated antiproliferative activities of 41.30 ± 3.93%, 67.76 ± 2.45%, and 75.93 ± 2.81% at 24, 48, and 72 h after the treatment, respectively. The cell apoptosis ratio at 24 h after the treatment is 32.6 ± 0.79%, which is significantly higher than other treatment groups such as PTX only and no-targeted PTX-loaded MBs (NPLMBs) with or without ultrasound mediation. Our experiment verifies the hypothesis that ultrasound mediation of ovarian cancer-targeted and drug-loaded MBs will enhance the PTX therapeutic efficiency.
authors.affiliation: Department of Obstetrics and Gynecology, Second Affiliated Hospital of Chongqing Medical University , Chongqing 400010, China.
authors.forename: Hongxia
authors.initials: H
authors.lastname: Liu
authors.forename: Shufang
authors.initials: S
authors.lastname: Chang
authors.forename: Jiangchuan
authors.initials: J
authors.lastname: Sun
authors.forename: Shenyin
authors.initials: S
authors.lastname: Zhu
authors.forename: Caixiu
authors.initials: C
authors.lastname: Pu
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhu
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.forename: Ronald X
authors.initials: RX
authors.lastname: Xu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects* / Q000528:radiation effects; D016503:Drug Delivery Systems; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D045423:Microbubbles; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D014465:Ultrasonics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008055:Lipids; D007987:Gonadotropin-Releasing Hormone; D017239:Paclitaxel