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Quercetin loaded folate targeted plasmonic silver nanoparticles for light activated chemo-photothermal therapy of DMBA induced breast cancer in Sprague Dawley rats

机译:槲皮素加载叶酸靶向等离子体纳米粒子纳米颗粒用于抗乳酪乳腺癌的乳腺癌的光活化化疗 - 光热疗法在Sprague Dawley大鼠

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摘要

Currently, the paucity of free drugs in conventional chemotherapy for breast-cancer curbs the desired therapeutic efficiency, often aggravating systemic toxicity. Quercetin (QRC) is a potential chemotherapeutic bio-flavonoid that is associated with poor hydrophilicity. In contrast to spherical silver nanoparticles (AgNPs), anisotropic AgNPs exhibit prominent plasmonic tunability in the near infrared (NIR) region allowing deep tissue penetration and endowing them with the ability to act as photothermal transducers as well. In this study, we optimized a simple and novel method for synthesizing folate-receptor-targeted-plasmonic silver-nanoparticles (QRC-FA-AgNPs) to serve as an efficient nanoscopic carrier system for breast cancer-cell targeted delivery of QRC and to induce photothermal therapy. A one-pot chemical synthesis method was followed for synthesizing the QRC-FA-AgNPs by finely tailoring the hydrogen bond between the reductant and stabilizer. Detailed characterization through UV-visible, near infrared (UV-vis-NIR) spectroscopy, Fourier transform infrared (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), selected area electron diffraction (SAED), and energy-dispersive X-ray spectroscopy (EDX), along with particle-size, zeta-potential analysis, drug-loading and release capacity and stability studies were also performed.In vitrotargeted cellular uptake, viability studies, chemo-photothermal efficacy, induction of apoptosis and the reactive oxygen species (ROS) generating potential were studied in the MDA-MB-231 cell-line andin vivoevaluation of the chemo-photothermal efficacy of QRC-FA-AgNPs was performed using a 7,12-dimethylbenz(a)anthracene (DMBA)-induced breast-carcinogenesis model in Sprague Dawley rats. Unlike conventional AgNPs, these novel pentagonal QRC-FA-AgNPs (<50 nm) manifested a robust plasmon tunability in the NIR (>800 nm) region. Detailedin vitroandin vivostudies revealed their active role in improving breast-cancer conditions by allowing controlled and targeted discharge of QRC at the tumor site, along with evoking hyperthermia under NIR laser irradiation that induced selective ablation of cancer cells. Following successful cellular internalization, the photothermal efficacy of QRC-FA-AgNPs supplemented their chemotherapeutic potency, allowing apoptosis and restraining the tumor growth. This current study highlighted the augmented efficacy of plasmonic QRC-FA-AgNPs in comparison to free quercetin, thus the development of a potential nanocarrier based on the pleiotropic function of plasmonic AgNPs may provide an efficient combined chemo-photothermal based strategy for the assassination of breast-cancer cells.
机译:目前,常规化疗对乳腺癌的缺乏药物的缺乏抑制所需的治疗效率,通常会加剧全身毒性。槲皮素(QRC)是一种潜在的化学治疗生物黄酮类化合物,其与亲水性不良相关。与球形银纳米颗粒(AgNP)相比,各向异性AgNP在近红外(NIR)区域中表现出突出的等离子体可调性,允许深层组织渗透并赋予它们作为光热换能器的能力。在这项研究中,我们优化用于合成的简单且新颖的方法叶酸受体靶向-电浆银纳米颗粒(QRC-FA-的AgNPs),以作为乳腺癌细胞的有效纳米载体系统靶向QRC和诱导的输送光热疗疗法。遵循一锅化学合成方法,通过在还原剂和稳定剂之间进行细化氢键来合成QRC-FA-AGNP。通过紫外线可见的详细表征,近红外(UV-Vis-NIR)光谱,傅里叶变换红外(FTIR),X射线衍射(XRD),透射电子显微镜(TEM),选择的区域电子衍射(SAED)和能量 - 还具有粒径,Zeta潜在分析,药物负荷和释放能力和稳定性研究的分散X射线光谱(EDX)。在玻璃体植物摄取,活力研究,化学光热功效,诱导细胞凋亡在MDA-MB-231细胞系中研究了活性氧物质(ROS)产生电位,使用7,12-二甲基苯并(A)蒽(1)蒽(a)蒽 - 均 - AgNP的化学光热功效。 DMBA) - 抑制Sprague Dawley大鼠的乳腺发生模型。与常规AgNP不同,这些新的五角形QRC-FA-AGNPS(<50nm)表现出NIR(> 800nm)区域的鲁棒等离子体可调性。 Ideroin Vitroandin Vivostudies通过允许在肿瘤部位允许QRC的控制和靶向QRC排出来揭示其在改善乳腺癌条件方面的积极作用,以及在鼻炎激光照射下引起热疗,诱导癌细胞的选择性消融。在成功的细胞内化之后,QRC-FA-AGNP的光热功效补充了其化学治疗性效力,允许细胞凋亡并限制肿瘤生长。该研究突出了比较与游离槲皮素相比,基于自由槲皮素的增强功效,从而基于等离子体AgNP的抗血压功能的潜在纳米载波的发展可以提供一种有效的Chemo-Photoholmal基于基于乳房的乳腺策略-Cancer细胞。

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  • 来源
    《RSC Advances》 |2020年第53期|共18页
  • 作者单位

    Birla Inst Technol Dept Pharm Sci &

    Technol Div Adv Pharmacol Ranchi 835215 Bihar India;

    Cent Univ South Bihar Sch Phys &

    Chem Sci Dept Chem Gaya 824236 India;

    Hebrew Univ Jerusalem Fritz Haber Ctr Mol Dynam Res Jerusalem Israel;

    Birla Inst Technol Dept Pharm Sci &

    Technol Div Adv Pharmacol Ranchi 835215 Bihar India;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 化学;
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