CS-PEG decorated PLGA nano-prototype for delivery of bioactive compounds: A novel approach for induction of apoptosis in HepG2 cell line

被引:65
作者
Abd-Rabou, Ahmed A. [1 ]
Ahmed, Hanaa H. [1 ]
机构
[1] Natl Res Ctr, Hormones Dept, Med Res Div, Giza 12622, Egypt
来源
ADVANCES IN MEDICAL SCIENCES | 2017年 / 62卷 / 02期
关键词
PLGA-CS-PEG nanoparticles; HepG2 cell line; Phytochemicals; Apoptosis; ACID INDUCES APOPTOSIS; PROSTATE-CANCER CELLS; IN-VITRO ANTIOXIDANT; PUNICA-GRANATUM L; FACTOR-KAPPA-B; ELLAGIC ACID; POMEGRANATE JUICE; ANTIPROLIFERATIVE ACTIVITY; BREAST-CANCER; SIGNALING PATHWAYS;
D O I
10.1016/j.advms.2017.01.003
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Purpose: Polymer-based nanoparticles are used as vectors for cancer drug delivery. The bioactive compounds (quercetin, ellagic acid and gallic acid) are well known to be not only antioxidants but also chemopreventive candidates against various types of cancers. To circumvent the low bioavailability and the short half-life time obstacles, we hypothesized a novel PLGA nano-platform functionalized with CS and PEG to encapsulate these phytochemicals. This encapsulation will protect the compounds from the phagocytic uptake and deliver PLGA-CS-PEG nano-prototype with high biodegradability and biosafety. Materials and methods: Three consequent types of PLGA-based nanocomposites were prepared and characterized. Furthermore, we investigated the newly synthesized nano-formulations against human hepatocellular carcinoma (HepG2) and colorectal cancer (HCT 116) cell lines using cell growth inhibition assays, followed by apoptosis and necrosis assays using flow cytometry to detect the underlying mechanism of HepG2 cell death. Results: Through Malvern Zeta Sizer, we recorded that the average diameters of the nano-prototypes ranged from 150 to 300 nm. The cytotoxic activity of quercetin, ellagic acid, and gallic acid-encapsulated PLGA, PLGA-CS, and PLGA-CS-PEG nano-prototypes it has been found that they reduce the IC50s of the HepG2 cells values by 2.2, 2.9, 2.8-folds, 1, 1.5, 2.7-folds, and 0.9, 0.7, 1.5-folds, respectively. Mechanistically, the nano-platforms of quercetin seem to be dependent on both apoptosis and necrosis, while those of ellagic acid and gallic acid are mainly dependent on apoptosis. Conclusions: CS-PEG-blended PLGA nano-delivery system of quercetin, ellagic acid and gallic acid can potentiate apoptosis-mediated cell death in HepG2 cell line. (C) 2017 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码:357 / 367
页数:11
相关论文
共 72 条
[21]   Evaluation of the bioavailability and metabolism in the rat of punicalagin, an antioxidant polyphenol from pomegranate juice [J].
Cerdá, B ;
Llorach, R ;
Cerón, JJ ;
Espín, JC ;
Tomás-Barberán, FA .
EUROPEAN JOURNAL OF NUTRITION, 2003, 42 (01) :18-28
[22]   Increase of Bax/Bcl-XL ratio and arrest of cell cycle by luteolin in immortalized human hepatoma cell line [J].
Chang, JS ;
Hsu, YL ;
Kuo, PL ;
Kuo, YC ;
Chiang, LC ;
Lin, CC .
LIFE SCIENCES, 2005, 76 (16) :1883-1893
[23]   Tissue inhibitor of metalloproteinase-1 promotes hematopoietic differentiation via caspase-3 upstream the MEKK1/MEK6/p38α pathway [J].
Dasse, E. ;
Bridoux, L. ;
Baranek, T. ;
Lambert, E. ;
Salesse, S. ;
Sowa, M. L. ;
Martiny, L. ;
Trentesaux, C. ;
Petitfrere, E. .
LEUKEMIA, 2007, 21 (04) :595-603
[24]   Ellagic acid induces apoptosis through inhibition of nuclear factor κB in pancreatic cancer cells [J].
Edderkaoui, Mouad ;
Odinokova, Irina ;
Ohno, Izumi ;
Gukovsky, Ilya ;
Go, Vay Liang W. ;
Pandol, Stephen J. ;
Gukovskaya, Anna S. .
WORLD JOURNAL OF GASTROENTEROLOGY, 2008, 14 (23) :3672-3680
[25]   The anthocyanin metabolites gallic acid, 3-O-methylgallic acid, and 2,4,6-trihydroxybenzaldehyde decrease human colon cancer cell viability by regulating pro-oncogenic signals [J].
Forester, Sarah C. ;
Choy, Ying Y. ;
Waterhouse, Andrew L. ;
Oteiza, Patricia I. .
MOLECULAR CARCINOGENESIS, 2014, 53 (06) :432-439
[26]   Antioxidant activity of pomegranate juice and its relationship with phenolic composition and processing [J].
Gil, MI ;
Tomás-Barberán, FA ;
Hess-Pierce, B ;
Holcroft, DM ;
Kader, AA .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2000, 48 (10) :4581-4589
[27]   THE CONTROLLED INTRAVENOUS DELIVERY OF DRUGS USING PEG-COATED STERICALLY STABILIZED NANOSPHERES [J].
GREF, R ;
DOMB, A ;
QUELLEC, P ;
BLUNK, T ;
MULLER, RH ;
VERBAVATZ, JM ;
LANGER, R .
ADVANCED DRUG DELIVERY REVIEWS, 1995, 16 (2-3) :215-233
[28]  
Heber D, 2011, HERBAL MED BIOMOLECU
[29]   Ellagic Acid Induces Apoptosis in TSGH8301 Human Bladder Cancer Cells Through the Endoplasmic Reticulum Stress- and Mitochondria-Dependent Signaling Pathways [J].
Ho, Chin-Chih ;
Huang, An-Cheng ;
Yu, Chun-Shu ;
Lien, Jin-Cherng ;
Wu, Shin-Hwar ;
Huang, Yi-Ping ;
Huang, Hui-Ying ;
Kuo, Jehn-Hwa ;
Liao, Wen-Yen ;
Yang, Jai-Sing ;
Chen, Po-Yuan ;
Chung, Jing-Gung .
ENVIRONMENTAL TOXICOLOGY, 2014, 29 (11) :1262-1274
[30]   PEGylated chitosan-based polymer micelle as an intracellular delivery carrier for anti-tumor targeting therapy [J].
Hu, Fu-Qiang ;
Meng, Pan ;
Dai, You-Qin ;
Du, Yong-Zhong ;
You, Jian ;
Wei, Xiao-Hong ;
Yuan, Hong .
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 2008, 70 (03) :749-757