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Biomaterials:姜黄素的超顺磁性氧化铁纳米颗粒增强了吉西他滨在胰腺癌中的治疗反应

2019-04-26 不详 网络

胰腺癌是一种复杂的疾病,可治疗纤维化肿瘤和侵袭性表型。吉西他滨(GEM)用作标准疗法,其产生化学抗性导致不良的患者结果。我们最近开发了姜黄素的超顺磁性氧化铁纳米颗粒(SPION)配方(SP-CUR),它是一种无毒的生物活性抗炎/抗癌剂,用于增强肿瘤的递送。在这项研究中,我们证明SP-CUR有效地将生物活性姜黄素递送到胰腺肿瘤,同时增强GEM摄取及其功效。机制揭示表明SP-CUR通过抑制声波刺猬(S

胰腺癌是一种复杂的疾病,可治疗纤维化肿瘤和侵袭性表型。吉西他滨(GEM)用作标准疗法,其产生化学抗性导致不良的患者结果。我们最近开发了姜黄素的超顺磁性氧化铁纳米颗粒(SPION)配方(SP-CUR),它是一种无毒的生物活性抗炎/抗癌剂,用于增强肿瘤的递送。

在这项研究中,我们证明SP-CUR有效地将生物活性姜黄素递送到胰腺肿瘤,同时增强GEM摄取及其功效。机制揭示表明SP-CUR通过抑制声波刺猬(SHH)途径和抑制双向肿瘤-基质细胞相互作用的致癌CXCR4/CXCL12信号轴来靶向肿瘤微环境。由于人核苷转运蛋白基因(DCK,hCNT)和阻断核糖核苷酸还原酶亚基(RRM1/RRM2)的上调,观察到GEM摄取增加。此外,SP-CUR和GEM的共同治疗通过调节多能性维持干细胞因子(Nanog,Sox2,c-Myc和Oct-4)和限制肿瘤球形成来靶向癌症干细胞。在原位小鼠模型中,在胰腺中发现SP-CUR的增强的积累,这增强了GEM以减少肿瘤生长和转移。对肿瘤组织的分析表明,通过原子力显微镜测量,该治疗抑制肿瘤基质(α-SMA,结蛋白和Hyluronic Acid)并诱导细胞僵硬度的变化。这伴随着SHH信号传导的关键细胞蛋白的改变,例如SHH,Gli-1,Gli-2,Sufu和NFĸB-65,如免疫印迹和免疫组织化学所示。

总之,这些结果表明SP-CUR具有很大的潜力,可用于未来临床用于胰腺癌的治疗。

原始出处:

Khan S, Setua S, et al., Superparamagnetic iron oxide nanoparticles of curcumin enhance gemcitabine therapeutic response in pancreatic cancer. Biomaterials. 2019 Apr 8;208:83-97. doi: 10.1016/j.biomaterials.2019.04.005.

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    2019-12-11 sunylz
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