Temperature-dependent and time-dependent effects of hyperthermia mediated by dextran-coated La0.7Sr0.3MnO3: in vitro studies
Authors Haghniaz R, Umrani R, Paknikar K
Received 26 November 2014
Accepted for publication 18 January 2015
Published 25 February 2015 Volume 2015:10(1) Pages 1609—1623
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 4
Editor who approved publication: Prof. Dr. Thomas J Webster
Reihaneh Haghniaz, Rinku D Umrani, Kishore M Paknikar
Centre for Nanobioscience, Agharkar Research Institute, Pune, Maharashtra, India
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.
Conclusion: Our findings indicate a potential use for Dex-LSMO-mediated hyperthermia in the treatment of melanoma and other types of cancer.
Keywords: hyperthermia, Dex-LSMO nanoparticles, heat shock proteins, melanoma, apoptosis
This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.Download Article [PDF] View Full Text [HTML][Machine readable]