关键词: docetaxel gold nanoparticles in vivo pancreatic cancer radiotherapy

来  源:   DOI:10.3390/pharmaceutics16060713   PDF(Pubmed)

Abstract:
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 μg/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.
摘要:
这项研究强调了将纳米技术与传统疗法结合在癌症治疗中的潜力,特别是对于像胰腺癌这样具有挑战性的病例。我们旨在通过研究金纳米颗粒(GNP)和多西他赛(DTX)作为潜在的放射增敏剂在体外和体内放疗(RT)中的协同作用来增强胰腺癌的治疗。利用MIAPaCa-2单培养球体模型和皮下植入MIAPaCa-2细胞的NRG小鼠,分别。用GNP(7.5μg/mL)处理球体,DTX(100nM),和使用6MV线性加速器的2GyRT。并行,小鼠接受GNP治疗(2mg/kg),DTX(6mg/kg),和5Gy的RT(6MV直线加速器)。体外结果表明,尽管RT和DTX减小了球状体大小并增加了DNADSB,DTX/RT/GNP的三重组合导致球体大小显着减少48%(p=0.05),DNADSB增加45%(p=0.05)。体内结果显示用(GNP/RT/DTX)治疗后20天肿瘤生长减少20%(p=0.05),并且小鼠中位存活增加。三联组合表现出协同效应,增强抗癌功效超越个体治疗,因此可用于改善放射治疗并潜在地减少不良反应。
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