title: Short-time focused ultrasound hyperthermia enhances liposomal doxorubicin delivery and antitumor efficacy for brain metastasis of breast cancer.
abstract: The blood-brain/tumor barrier inhibits the uptake and accumulation of chemotherapeutic drugs. Hyperthermia can enhance the delivery of chemotherapeutic agent into tumors. In this study, we investigated the effects of short-time focused ultrasound (FUS) hyperthermia on the delivery and therapeutic efficacy of pegylated liposomal doxorubicin (PLD) for brain metastasis of breast cancer. Murine breast cancer 4T1-luc2 cells expressing firefly luciferase were injected into female BALB/c mice striatum tissues and used as a brain metastasis model. The mice were intravenously injected with PLD (5 mg/kg) with/without 10-minute transcranial FUS hyperthermia on day 6 after tumor implantation. The amounts of doxorubicin accumulated in the normal brain tissues and tumor tissues with/without FUS hyperthermia were measured using fluorometry. The tumor growth for the control, hyperthermia, PLD, and PLD + hyperthermia groups was measured using an IVIS spectrum system every other day from day 3 to day 11. Cell apoptosis and tumor characteristics were assessed using immunohistochemistry. Short-time FUS hyperthermia was able to significantly enhance the PLD delivery into brain tumors. The tumor growth was effectively inhibited by a single treatment of PLD + hyperthermia compared with both PLD alone and short-time FUS hyperthermia alone. Immunohistochemical examination further demonstrated the therapeutic efficacy of PLD plus short-time FUS hyperthermia for brain metastasis of breast cancer. The application of short-time FUS hyperthermia after nanodrug injection may be an effective approach to enhance nanodrug delivery and improve the treatment of metastatic cancers.
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, Taipei, Taiwan.
authors.forename: Sheng-Kai
authors.initials: SK
authors.lastname: Wu
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, Taipei, Taiwan.
authors.forename: Chi-Feng
authors.initials: CF
authors.lastname: Chiang
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, Taipei, Taiwan ; Department of Neurosurgery, Cheng-Hsin General Hospital, Taipei, Taiwan.
authors.forename: Yu-Hone
authors.initials: YH
authors.lastname: Hsu
authors.affiliation: Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Tzu-Hung
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Houng-Chi
authors.initials: HC
authors.lastname: Liou
authors.affiliation: Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Wen-Mei
authors.initials: WM
authors.lastname: Fu
authors.affiliation: Institute of Biomedical Engineering, College of Medicine and College of Engineering, Taipei, Taiwan ; Institute of Biomedical Engineering and Nanomedicine, National Health Research Institutes, Miaoli, Taiwan.
authors.forename: Win-Li
authors.initials: WL
authors.lastname: Lin
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry / Q000493:pharmacokinetics; D005260:Female; D006979:Hyperthermia, Induced / Q000379:methods*; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D045423:Microbubbles; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D014464:Ultrasonic Therapy
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin
keywords: brain metastasis of breast cancer; focused ultrasound (FUS); hyperthermia; pegylated liposomal doxorubicin (PLD)