title: Temperature-dependent and time-dependent effects of hyperthermia mediated by dextran-coated La0.7Sr0.3MnO3: in vitro studies.
abstract: BACKGROUND
  The purpose of this study was to investigate the therapeutic efficacy of dextran-coated (Dex) La0.7Sr0.3MnO3 (LSMO) nanoparticles-mediated hyperthermia at different temperatures (43°C, 45°C, and 47°C) based on cell killing potential and induction of heat shock proteins in a murine melanoma cell (B16F1) line.
  
  
  METHODS
  LSMO nanoparticles were synthesized by a citrate-gel method and coated with dextran. B16F1 cells were exposed to the Dex-LSMO nanoparticles and heated using a radiofrequency generator. After heating, the morphology and topology of the cells were investigated by optical microscopy and atomic force microscopy. At 0 hours and 24 hours post heating, cells were harvested and viability was analyzed by the Trypan blue dye exclusion method. Apoptosis and DNA fragmentation were assessed by terminal deoxynucleotidyl transferase-dUTP nick end labeling (TUNEL) assay and agarose gel electrophoresis, respectively. An enzyme-linked immunosorbent assay was used to quantify heat shock protein levels.
  
  
  RESULTS
  Our data indicate that cell death and induction of heat shock proteins in melanoma cells increased in a time-dependent and temperature-dependent manner, particularly at temperatures higher than 43°C. The mode of cell death was found to be apoptotic, as evident by DNA fragmentation and TUNEL signal. A minimum temperature of 45°C was required to irreversibly alter cell morphology, significantly reduce cell viability, and result in 98% apoptosis. Repeated cycles of hyperthermia could induce higher levels of heat shock proteins (more favorable for antitumor activity) when compared with a single cycle.
  
  
  CONCLUSIONS
  Our findings indicate a potential use for Dex-LSMO-mediated hyperthermia in the treatment of melanoma and other types of cancer.
authors.affiliation: Centre for Nanobioscience, Agharkar Research Institute, Pune, Maharashtra, India.
authors.forename: Reihaneh
authors.initials: R
authors.lastname: Haghniaz
authors.affiliation: Centre for Nanobioscience, Agharkar Research Institute, Pune, Maharashtra, India.
authors.forename: Rinku D
authors.initials: RD
authors.lastname: Umrani
authors.affiliation: Centre for Nanobioscience, Agharkar Research Institute, Pune, Maharashtra, India.
authors.forename: Kishore M
authors.initials: KM
authors.lastname: Paknikar
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D003911:Dextrans / Q000737:chemistry*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006358:Hot Temperature; D008670:Metals / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D003911:Dextrans; D006360:Heat-Shock Proteins; D008670:Metals
keywords: Dex-LSMO nanoparticles; apoptosis; heat shock proteins; hyperthermia; melanoma