title: Hollow iron-silica nanoshells for enhanced high intensity focused ultrasound.
abstract: BACKGROUND
  High intensity-focused ultrasound (HIFU) is an alterative ablative technique currently being investigated for local treatment of breast cancer and fibroadenomas. Current HIFU therapies require concurrent magnetic resonance imaging monitoring. Biodegradable 500 nm perfluoropentane-filled iron-silica nanoshells have been synthesized as a sensitizing agent for HIFU therapies, which aid both mechanical and thermal ablation of tissues. In low duty cycle high-intensity applications, rapid tissue damage occurs from mechanical rather than thermal effects, which can be monitored closely by ultrasound obviating the need for concurrent magnetic resonance imaging.
  
  
  METHODS
  Iron-silica nanoshells were synthesized by a sol-gel method on polystyrene templates and calcined to yield hollow nanoshells. The nanoshells were filled with perfluoropentane and injected directly into excised human breast tumor, and intravenously (IV) into healthy rabbits and Py8119 tumor-bearing athymic nude mice. HIFU was applied at 1.1 MHz and 3.5 MPa at a 2% duty cycle to achieve mechanical ablation.
  
  
  RESULTS
  Ex vivo in excised rabbit livers, the time to visually observable damage with HIFU was 20 s without nanoshells and only 2 s with nanoshells administered IV before sacrifice. Nanoshells administered IV into nude mice with xenograft tumors were activated in vivo by HIFU 24 h after administration. In this xenograft model, applied HIFU resulted in a 13.6 ± 6.1 mm(3) bubble cloud with the IV injected particles and no bubble cloud without particles.
  
  
  CONCLUSIONS
  Iron-silica nanoshells can reduce the power and time to perform HIFU ablative therapy and can be monitored by ultrasound during low duty cycle operation.
authors: Materials Science and Engineering Program, University of California, San Diego.
authors: Alexander
authors: A
authors: Liberman
authors: Department of Radiology, University of California, San Diego.
authors: Zhe
authors: Z
authors: Wu
authors: Department of Radiology, University of California, San Diego.
authors: Christopher V
authors: CV
authors: Barback
authors: Department of Nanoengineering, University of California, San Diego.
authors: Robert D
authors: RD
authors: Viveros
authors: Department of Nanoengineering, University of California, San Diego.
authors: James
authors: J
authors: Wang
authors: Department of Pathology, University of California, San Diego.
authors: Lesley G
authors: LG
authors: Ellies
authors: Department of Radiology, University of California, San Diego; Moores Cancer Center, University of California, San Diego.
authors: Robert F
authors: RF
authors: Mattrey
authors: Department of Chemistry and Biochemistry, University of California, San Diego.
authors: William C
authors: WC
authors: Trogler
authors: Department of Chemistry and Biochemistry, University of California, San Diego.
authors: Andrew C
authors: AC
authors: Kummel
authors: Moores Cancer Center, University of California, San Diego; Department of Surgery, University of California, San Diego. Electronic address: slblair@ucsd.edu.
authors: Sarah L
authors: SL
authors: Blair
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000628:therapy*; D005260:Female; D018226:Fibroadenoma / Q000628:therapy; D005466:Fluorocarbons; D057086:High-Intensity Focused Ultrasound Ablation / Q000295:instrumentation*; D006801:Humans; D007501:Iron; D051379:Mice; D008819:Mice, Nude; D057145:Nanoshells / Q000627:therapeutic use*; D011817:Rabbits; D012822:Silicon Dioxide; D010420:Pentanes
chemical_list: D005466:Fluorocarbons; D007501:Iron; D012822:Silicon Dioxide; C008806:perfluoropentane; D010420:Pentanes
keywords: Breast cancer; HIFU; Histotripsy; Nanoparticles; Silica