Dual enhancement in the radiosensitivity of prostate cancer through nanoparticles and chemotherapeutics

Cancer Nanotechnology

Research

Jessica Morgan¹  Kyle Bromma²  Nolan Jackson²  Abdulaziz Alhussan²  Wayne Beckham³  Devika Basnagge Chithrani⁴  Yasmin Zahra⁵  Steven Herchko⁵  Yuri Mackeyev⁶  Iona Hill⁶  Belal Abousaida⁶  Sunil Krishnan⁷ 

[1] Department of Biochemistry and Microbiology, University of Victoria, V8P 5C2, Victoria, BC, Canada;Trev and Joyce Deeley Research Centre, BC Cancer, V8R 6V5, Victoria, BC, Canada;Department of Physics and Astronomy, University of Victoria, V8P 5C2, Victoria, BC, Canada;Department of Physics and Astronomy, University of Victoria, V8P 5C2, Victoria, BC, Canada;British Columbia Cancer-Victoria, V8R 6V5, Victoria, BC, Canada;Department of Physics and Astronomy, University of Victoria, V8P 5C2, Victoria, BC, Canada;Centre for Advanced Materials and Related Technologies, Department of Chemistry, University of Victoria, V8P 5C2, Victoria, BC, Canada;Division of Medical Sciences, University of Victoria, V8P 5C2, Victoria, BC, Canada;Department of Computer Science, Mathematics, Physics and Statistics, Okanagan Campus, University of British Columbia, V1V 1V7, Kelowna, BC, Canada;Department of Radiation Oncology, Mayo Clinic, 32224, Jacksonville, FL, USA;Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center, 77030, Houston, TX, USA;Vivian L. Smith Department of Neurosurgery, The University of Texas Health Science Center, 77030, Houston, TX, USA;Department of Radiation Oncology, Mayo Clinic, 32224, Jacksonville, FL, USA;

关键词: Gold nanoparticles;    Docetaxel;    Prostate cancer;    Radiotherapy;    Radiosensitivity;   

DOI  :  10.1186/s12645-023-00228-0

 received in 2023-06-20, accepted in 2023-09-20,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundRadiotherapy (RT) is an essential component in the treatment regimens for many cancer patients. However, the dose escalation required to improve curative results is hindered due to the normal tissue toxicity that is induced. The introduction of radiosensitizers to RT treatment is an avenue that is currently being explored to overcome this issue. By introducing radiosensitizers into tumor sites, it is possible to preferentially enhance the local dose deposited. Gold nanoparticles (GNPs) are a potential candidate that have shown great promise in increasing the radiosensitivity of cancer cells through an enhancement in DNA damage. Furthermore, docetaxel (DTX) is a chemotherapeutic agent that arrests cells in the G2/M phase of the cell cycle, the phase most sensitive to radiation damage. We hypothesized that by incorporating DTX to GNP-enhanced radiotherapy treatment, we could further improve the radiosensitization experienced by cancer cells. To assess this strategy, we analyzed the radiotherapeutic effects on monolayer cell cultures in vitro, as well as on a mice prostate xenograft model in vivo while using clinically feasible concentrations for both GNPs and DTX.ResultsThe introduction of DTX to GNP-enhanced radiotherapy further increased the radiotherapeutic effects experienced by cancer cells. A 38% increase in DNA double-strand breaks was observed with the combination of GNP/DTX vs GNP alone after a dose of 2 Gy was administered. In vivo results displayed significant reduction in tumor growth over a 30-day observation period with the treatment of GNP/DTX/RT when compared to GNP/RT after a single 5 Gy dose was given to mice. The treatment strategy also resulted in 100% mice survival, which was not observed for other treatment conditions.ConclusionsIncorporating DTX to work in unison with GNPs and RT can increase the efficacy of RT treatment. Our study suggests that the treatment strategy could improve tumor control through local dose enhancement. As the concentrations used in this study are clinically feasible, there is potential for this strategy to be translated into clinical settings.

【 授权许可】

CC BY   
© Springer-Verlag GmbH Austria, part of Springer Nature 2023

【 图 表 】

Fig. 3

Fig. 2

Fig. 4

Fig. 2

Fig. 2

Fig. 1

12888_2023_5172_Article_IEq44.gif