In Vitro and In Vivo Synergetic Radiotherapy with Gold Nanoparticles and Docetaxel for Pancreatic Cancer

被引:4
作者
Alhussan, Abdulaziz [1 ]
Jackson, Nolan [1 ]
Chow, Norman [2 ]
Gete, Ermias [3 ,4 ]
Wretham, Nicole [2 ]
Dos Santos, Nancy [2 ]
Beckham, Wayne [1 ,5 ]
Duzenli, Cheryl [3 ,4 ]
Chithrani, Devika B. [1 ,5 ,6 ,7 ,8 ]
机构
[1] Univ Victoria, Dept Phys & Astron, Victoria, BC V8P 5C2, Canada
[2] British Columbia Canc Vancouver, Dept Expt Therapeut, BC V5Z IL3, Vancouver, BC, Canada
[3] British Columbia Canc Vancouver, Radiat Oncol, Vancouver, BC V5Z 4E6, Canada
[4] Univ British Columbia, Dept Phys & Astron, Vancouver, BC V6T 1Z1, Canada
[5] British Columbia Canc Victoria, Radiat Oncol, Victoria, BC V8R 6V5, Canada
[6] Univ Victoria, Ctr Adv Mat & Related Technol, Dept Chem, Victoria, BC V8P 5C2, Canada
[7] Univ Victoria, Dept Med Sci, Victoria, BC V8P 5C2, Canada
[8] Univ British Columbia, Dept Comp Sci Math Phys & Stat, Okanagan Campus, Kelowna, BC V1V 1V7, Canada
基金
加拿大创新基金会; 美国国家卫生研究院; 加拿大自然科学与工程研究理事会;
关键词
gold nanoparticles; docetaxel; radiotherapy; pancreatic cancer; in vivo; RADIATION-THERAPY; CELLULAR UPTAKE; TUMORS; ENHANCE; RADIOSENSITIZERS; EPIDEMIOLOGY; TRANSPORT; DELIVERY;
D O I
10.3390/pharmaceutics16060713
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
This research underscores the potential of combining nanotechnology with conventional therapies in cancer treatment, particularly for challenging cases like pancreatic cancer. We aimed to enhance pancreatic cancer treatment by investigating the synergistic effects of gold nanoparticles (GNPs) and docetaxel (DTX) as potential radiosensitizers in radiotherapy (RT) both in vitro and in vivo, utilizing a MIA PaCa-2 monoculture spheroid model and NRG mice subcutaneously implanted with MIA PaCa-2 cells, respectively. Spheroids were treated with GNPs (7.5 mu g/mL), DTX (100 nM), and 2 Gy of RT using a 6 MV linear accelerator. In parallel, mice received treatments of GNPs (2 mg/kg), DTX (6 mg/kg), and 5 Gy of RT (6 MV linear accelerator). In vitro results showed that though RT and DTX reduced spheroid size and increased DNA DSBs, the triple combination of DTX/RT/GNPs led to a significant 48% (p = 0.05) decrease in spheroid size and a 45% (p = 0.05) increase in DNA DSBs. In vivo results showed a 20% (p = 0.05) reduction in tumor growth 20 days post-treatment with (GNPs/RT/DTX) and an increase in mice median survival. The triple combination exhibited a synergistic effect, enhancing anticancer efficacy beyond individual treatments, and thus could be employed to improve radiotherapy and potentially reduce adverse effects.
引用
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页数:17
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