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白藜芦醇苷包裹的聚乳酸-羟基乙酸共聚物纳米制剂通过抑制细胞增殖对抗7,12-二甲基苯并[a]蒽介导的实验性致癌作用。

Polydatin Encapsulated Poly [Lactic-co-glycolic acid] Nanoformulation Counteract the 7,12-Dimethylbenz[a] Anthracene Mediated Experimental Carcinogenesis through the Inhibition of Cell Proliferation.

作者信息

Vijayalakshmi Sankaran, Mariadoss Arokia Vijaya Anand, Ramachandran Vinayagam, Shalini Vijayakumar, Agilan Balupillai, Sangeetha Casimeer C, Balu Periyasamy, Kotakadi Venkata Subbaih, Karthikkumar Venkatachalam, Ernest David

机构信息

Department of Biotechnology, Thiruvalluvar University, Serkadu, Vellore 632 115, Tamilnadu, India.

Department of Physics, Sri Padmavati Mahila Visvavidyalayam, Tirupati 517502, Andra Pradesh, India.

出版信息

Antioxidants (Basel). 2019 Sep 5;8(9):375. doi: 10.3390/antiox8090375.

DOI:10.3390/antiox8090375
PMID:31491872
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6770361/
Abstract

In the present study, the authors have attempted to fabricate Polydatin encapsulated Poly [lactic-co-glycolic acid] (POL-PLGA-NPs) to counteract 7,12-dimethyl benzyl anthracene (DMBA) promoted buccal pouch carcinogenesis in experimental animals. The bio-formulated POL-PLGA-NPs were characterized by dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRD) pattern analysis, and transmission electron microscope (TEM). In addition, the nano-chemopreventive potential of POL-PLGA-NPs was assessed by scrutinizing the neoplastic incidence and analyzing the status of lipid peroxidation, antioxidants, phase I, phase II detoxification status, and histopathological changes and in DMBA-treated animals. In golden Syrian hamsters, oral squamous cell carcinoma (OSCC) was generated by painting with 0.5% DMBA in liquid paraffin three times a week for 14 weeks. After 100% tumor formation was observed, high tumor volume, tumor burden, and altered levels of biochemical status were observed in the DMBA-painted hamsters. Intra-gastric administration of varying concentration of POL-PLGA-NPs (7.5, 15, and 30 mg/kg b.wt) to DMBA-treated hamsters assumedly prevents oncological incidences and restores the status of the biochemical markers. It also significantly enhances the apoptotic associated and inhibits the cancer cell proliferative markers expression (p53, Bax, Bcl-2, cleaved caspase 3, cyclin-D1). The present study reveals that POL-PLGA-NPs is a penitential candidate for nano-chemopreventive, anti-lipid peroxidative, and antioxidant potential, and also has a modulating effect on the phase I and Phase II detoxification system, which is associated with reduced cell proliferation and induced apoptosis in experimental oral carcinogenesis.

摘要

在本研究中,作者试图制备白藜芦醇苷包裹的聚乳酸-羟基乙酸共聚物纳米粒(POL-PLGA-NPs),以对抗7,12-二甲基苯并蒽(DMBA)诱导的实验动物颊囊癌变。通过动态光散射(DLS)、傅里叶变换红外(FTIR)光谱、X射线粉末衍射(XRD)图谱分析和透射电子显微镜(TEM)对生物制剂POL-PLGA-NPs进行了表征。此外,通过检查肿瘤发生率以及分析脂质过氧化、抗氧化剂、I相、II相解毒状态和组织病理学变化情况,评估了POL-PLGA-NPs在DMBA处理动物中的纳米化学预防潜力。在金黄叙利亚仓鼠中,通过每周三次用0.5% DMBA的液体石蜡溶液涂抹14周来诱发口腔鳞状细胞癌(OSCC)。在观察到100%肿瘤形成后,DMBA涂抹组仓鼠出现了高肿瘤体积、肿瘤负荷以及生化状态改变。给DMBA处理的仓鼠胃内给予不同浓度的POL-PLGA-NPs(7.5、15和30 mg/kg体重),推测可预防肿瘤发生并恢复生化标志物的状态。它还显著增强凋亡相关指标并抑制癌细胞增殖标志物的表达(p53、Bax、Bcl-2、裂解的半胱天冬酶3、细胞周期蛋白D1)。本研究表明,POL-PLGA-NPs是一种具有纳米化学预防、抗脂质过氧化和抗氧化潜力的潜在候选物,并且对I相和II相解毒系统具有调节作用,这与实验性口腔癌发生中细胞增殖减少和凋亡诱导有关。

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