叶酸偶联壳聚糖包覆的 PLGA 载姜黄素纳米粒对脑胶质瘤癌细胞氧化还原系统的影响。
Effect of folic acid-linked chitosan-coated PLGA-based curcumin nanoparticles on the redox system of glioblastoma cancer cells.
机构信息
Clinical Biochemistry Department, Medical Faculty, Shahrood Azad University, Shahrood, Iran.
Department of Clinical Biochemistry, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
出版信息
Phytochem Anal. 2023 Dec;34(8):950-958. doi: 10.1002/pca.3263. Epub 2023 Jul 18.
OBJECTIVES
Oxidative stress is one of the carcinogenic mechanisms underlying the development of glioblastoma multiforme (GBM), a highly aggressive brain tumor type associated with poor prognosis. Curcumin is known to be an efficient antioxidant, anti-inflammatory, and anticancer compound. However, its poor solubility in water, inappropriate pharmacokinetics, and low bioavailability limit its use as an antitumor drug. We prepared PLGA-based curcumin nanoparticles changed with folic acid and chitosan (curcumin-PLGA-CS-FA) and evaluated its effects on GBM tumor cells' redox status.
METHODS
The nanoprecipitation method was used to synthesize CU nanoparticles (CU-NPs). The size, morphology, and stability were characterized by DLS, SEM, and zeta potential analysis, respectively. The CU-NPs' toxic properties were studied by MTT assay and measuring the intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) concentrations. The study was completed by measuring the gene expression levels and activity of superoxide dismutase, catalase, glutaredoxin, and thioredoxin antioxidant enzymes.
RESULTS
The size, polydispersity index, and zeta potential of CU-NPs were 77.27 nm, 0.29, and -22.45 mV, respectively. The encapsulation efficiency was approximately 98%. Intracellular ROS and MDA levels decreased after CU-NP treatment. Meanwhile, the CU-NPs increased gene expression and activity of superoxide dismutase, catalase, glutaredoxin, and thioredoxin antioxidant enzymes.
CONCLUSION
CU-NPs might be effective in the prevention and treatment of glioblastoma cancer by modulating the antioxidant-oxidant balance.
目的
氧化应激是多形性胶质母细胞瘤（GBM）发展的致癌机制之一，GBM 是一种侵袭性很强的脑肿瘤，预后不良。姜黄素是一种有效的抗氧化剂、抗炎剂和抗癌化合物。然而，其在水中的溶解度低、药代动力学不合适和生物利用度低限制了其作为抗肿瘤药物的应用。我们制备了基于 PLGA 的姜黄素纳米粒，并用叶酸和壳聚糖进行了修饰（姜黄素-PLGA-CS-FA），并评估了其对 GBM 肿瘤细胞氧化还原状态的影响。
方法
采用纳米沉淀法合成 CU 纳米粒（CU-NPs）。分别采用 DLS、SEM 和 zeta 电位分析对其粒径、形态和稳定性进行了表征。通过 MTT 检测和测量细胞内活性氧（ROS）和丙二醛（MDA）浓度来研究 CU-NPs 的毒性。通过测量超氧化物歧化酶、过氧化氢酶、谷胱甘肽还原酶和硫氧还蛋白抗氧化酶的基因表达水平和活性来完成研究。
结果
CU-NPs 的粒径、多分散指数和 zeta 电位分别为 77.27nm、0.29 和-22.45mV，包封效率约为 98%。CU-NP 处理后细胞内 ROS 和 MDA 水平降低。同时，CU-NPs 增加了超氧化物歧化酶、过氧化氢酶、谷胱甘肽还原酶和硫氧还蛋白抗氧化酶的基因表达和活性。
结论
CU-NPs 通过调节抗氧化-氧化平衡，可能对预防和治疗胶质母细胞瘤有效。
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