title: Heat shock protein expression and temperature distribution in prostate tumours treated with laser irradiation and nanoshells.
abstract: OBJECTIVE
  Sub-lethal temperature elevations in the tumour incurred during laser cancer therapy can induce heat shock protein (HSP) expression leading to enhanced tumour survival and recurrence. Nanoshells utilised in combination with laser therapy can potentially enable selective heat deposition, greater thermal injury, and diminished HSP expression in the tumour. The study objective was to measure the distribution of temperature and HSP expression in prostate tumours in response to laser therapy alone or with nanoshells to determine if these combinatorial therapies can minimise HSP expression.
  
  
  METHODS
  PC3 cells were inoculated in the backs of CB17-Prkd c SCID/J mice and treated with external laser irradiation (wavelength of 810 nm, irradiance of 5 W/cm(2), spot size of 5 mm, and heating duration of 3 min) alone or in combination with gold nanoshells (diameter of 55 nm and outer gold shell thickness of 10 nm) introduced into the tumour 24 h prior to laser treatment. Magnetic resonance temperature imaging was used to measure the distribution of temperature elevation in the tumours during laser treatment. Tumours were sectioned 16 h following laser treatment, stained for Hsp27 and Hsp70, imaged with a confocal microscope, and HSP expression levels were quantified as a function of depth in the tumours.
  
  
  RESULTS
  Maximum temperature elevations at the tumour surface were 28°C for laser treatment only and 50°C for laser heating in combination with gold nanoshells. Laser therapy alone caused significant induction of HSP expression in the first few millimeters of the tumour depth, whereas decreasing HSP expression occurred with greater tumour depth. Tumours treated with laser and nanoshells experienced substantial temperatures (73-78°C) at the tumour surface and temperatures greater than 53°C in the first few millimeters which eliminated HSP expression.
  
  
  CONCLUSIONS
  Inclusion of nanoshells in laser therapy can provide a mechanism for enhancing heat deposition capable of eliminating HSP expression within a larger tumour region compared to laser heating alone.
authors.affiliation: Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences and Department of Mechanical Engineering, Blacksburg, VA 24060, USA. mnr@vt.edu
authors.forename: Marissa Nichole
authors.initials: MN
authors.lastname: Rylander
authors.forename: R Jason
authors.initials: RJ
authors.lastname: Stafford
authors.forename: John
authors.initials: J
authors.lastname: Hazle
authors.forename: Jon
authors.initials: J
authors.lastname: Whitney
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Diller
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006046:Gold; D055551:HSP27 Heat-Shock Proteins / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D053685:Laser Therapy; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D057145:Nanoshells / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000601:surgery; D023041:Xenograft Model Antitumor Assays
chemical_list: D055551:HSP27 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D006046:Gold