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负载槲皮素的叶酸靶向等离子体银纳米颗粒用于光激活化学-光热疗法治疗SD大鼠二甲基苯并蒽诱导的乳腺癌

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

作者信息

Bose Pritha, Priyam Amiya, Kar Rajiv, Pattanayak Shakti P

机构信息

Division of Advanced Pharmacology, Department of Pharm. Sciences & Technology, Birla Institute of Technology Mesra Ranchi-835215 India.

Department of Chemistry, School of Physical and Chemical Sciences, Central University of South Bihar Gaya 824236 India.

出版信息

RSC Adv. 2020 Aug 28;10(53):31961-31978. doi: 10.1039/d0ra05793b. eCollection 2020 Aug 26.

Abstract

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. targeted 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 and evaluation of the chemo-photothermal efficacy of QRC-FA-AgNPs was performed using a 7,12-dimethylbenz()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. Detailed and studies 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.

摘要

目前,乳腺癌传统化疗中游离药物的匮乏限制了预期的治疗效果,常常加剧全身毒性。槲皮素(QRC)是一种具有潜在化疗作用的生物类黄酮,但亲水性较差。与球形银纳米颗粒(AgNPs)相比,各向异性AgNPs在近红外(NIR)区域表现出显著的等离子体可调性,能够实现深部组织穿透,还赋予它们作为光热换能器的能力。在本研究中,我们优化了一种简单新颖的方法来合成叶酸受体靶向等离子体银纳米颗粒(QRC-FA-AgNPs),用作乳腺癌细胞靶向递送QRC的高效纳米载体系统,并诱导光热疗法。采用一锅化学合成法,通过精细调整还原剂和稳定剂之间的氢键来合成QRC-FA-AgNPs。还通过紫外-可见、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)、选区电子衍射(SAED)和能量色散X射线光谱(EDX)进行了详细表征,同时进行了粒径、zeta电位分析、载药和释药能力以及稳定性研究。在MDA-MB-231细胞系中研究了靶向细胞摄取、活力研究、化学-光热疗效、凋亡诱导以及活性氧(ROS)生成潜力,并使用7,12-二甲基苯并(a)蒽(DMBA)诱导的Sprague Dawley大鼠乳腺癌模型评估了QRC-FA-AgNPs的化学-光热疗效。与传统AgNPs不同,这些新型五角形QRC-FA-AgNPs(<50 nm)在近红外(>800 nm)区域表现出强大的等离子体可调性。详细的[此处原文可能缺失部分内容]和研究表明,它们通过在肿瘤部位实现QRC的可控靶向释放,以及在近红外激光照射下引发热疗从而诱导癌细胞选择性消融,在改善乳腺癌病情方面发挥了积极作用。在成功实现细胞内化后,QRC-FA-AgNPs的光热疗效增强了其化疗效力,促进了凋亡并抑制了肿瘤生长。本研究强调了等离子体QRC-FA-AgNPs与游离槲皮素相比具有更高的疗效,因此基于等离子体AgNPs多效功能开发潜在的纳米载体可能为杀死乳腺癌细胞提供一种高效的联合化学-光热策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2db0/9056571/0c6830a576e6/d0ra05793b-f1.jpg

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