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Photothermal therapy of prostate cancer using gold nanoparticles

University of British Columbia

Prostate cancer is the most common cancer in men. Many existing treatments for prostate cancer are often not completely effective and/or are invasive. Multimodal or combination therapy represents a promising new method to fight disease. Therefore, a combination of different therapeutic strategies may be the best alternative to improve treatment outcomes for prostate cancer. Photothermal therapy combined with gene and chemotherapy was proposed as a novel approach to treatment. In this work, photothermal therapy with gold nanoparticles and near infrared laser (NIR) irradiation, and gene therapy targeting heat shock protein 27 using antisense oligonucleotides (ASO), was investigated. Four types of small (<100nm), NIR absorbing gold nanoparticles (nanoshells, nanorods, core-corona and hollow nanoshells) were synthesized using wet chemical methods and characterized by transmission electron microscopy, dynamic light scattering and UV-vis spectroscopy. Their synthesis and properties were evaluated, to determine their feasibility as a photothermal agent for clinical applications. In vitro cellular uptake studies of the nanoparticles into prostate cancer cell lines, LNCaP and PC3, were measured using light scattering microscopy. The effect of ASO on hyperthermia of cancer cells was investigated using cell viability assays to determine if heat sensitization was possible. Photothermal treatment of the cancer cell lines using synthesized gold nanoparticles was evaluated and compared with commercially available Auroshell® particles. The effect of photothermal treatment and ASO in vitro was determined by measuring cell viability. A preliminary in vivo model study was performed to examine treatment conditions and heat generation. Small gold nanoshells (40nm) had good photothermal properties and the greatest cellular uptake, and were used in photothermal studies. Under 4W laser irradiation, an increase in temperature of 12°C and decrease in cell viability of up to 70% were obtained. Comparative work suggests that the 40nm gold nanoshells have a higher therapeutic efficiency than the larger Auroshell® particles. It is uncertain from the present study, if the addition of ASO can sensitize prostate cancer cells to hyperthermia. However, ASO treatment had a concentration dependent effect on cell viability, which could be useful to treatment goals. In vivo, localized high temperatures were generated with gold nanoparticles at low laser powers.

Text

2010-11-29

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/30161

Chemistry

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/