Geethakumari Deepa, Bhaskaran Sathyabhama Anoop, Raji Sathyan Krishnapriya, Mohandas Dhaneesha, Somasekharan Jisha V, Thavarool Puthiyedathu Sajeevan
National Centre for Aquatic Animal Health, Cochin University of Science and Technology, Fine Arts Avenue, Kochi 682 016, Kerala, India.
Research and Post Graduate Department of Chemistry, MES Keveeyam College, Valanchery 676552, Kerala, India.
Int J Biol Macromol. 2022 Feb 28;199:150-161. doi: 10.1016/j.ijbiomac.2021.12.070. Epub 2021 Dec 30.
Anticancer drug cytarabine, has been widely used for treating haematological malignancies while it has minimal activity against solid tumours, which demands continuous infusion leading to high dose cytarabine toxicity. In this study, folate conjugated chitosan nanoparticles (FCCNP) were used for targeted delivery of cytarabine in breast adenocarcinoma cell lines by making use of the overexpressed folate receptors on the surface of MCF-7. Folate was conjugated to chitosan using carbodiimide. FCCNPs show spherical morphology with a size of<50 nm. Zeta potential of + 45.2 mV and PDI of 0.98 from DLS measurement confirms a stable monodisperse nanoformulation. Cytotoxicity was studied in folate receptor positive, MCF-7 and folate receptor negative, A-549 cell lines. Increased cellular uptake of the drug incorporated nanoparticles was confirmed in MCF-7 cells with fluorophore, squaraine 650 compared to A-549 cells. The relative fold of expression of genes involved in apoptosis such as bax, cyt c and cas 9 were upregulated. The present in vitro study confirms improved cytotoxicity of cytarabine folate conjugated chitosan nanoparticles in MCF-7 cells.
抗癌药物阿糖胞苷已被广泛用于治疗血液系统恶性肿瘤,但其对实体瘤的活性极小,这需要持续输注,导致高剂量阿糖胞苷毒性。在本研究中,利用MCF-7表面过表达的叶酸受体,将叶酸偶联壳聚糖纳米粒(FCCNP)用于阿糖胞苷在乳腺癌细胞系中的靶向递送。使用碳二亚胺将叶酸与壳聚糖偶联。FCCNPs呈球形,尺寸小于50nm。动态光散射测量的zeta电位为+45.2mV,多分散指数为0.9,证实了稳定的单分散纳米制剂。在叶酸受体阳性的MCF-7和叶酸受体阴性的A-549细胞系中研究了细胞毒性。与A-549细胞相比,用荧光团方酸菁650证实MCF-7细胞中药物包载纳米粒的细胞摄取增加。参与凋亡的基因如bax、细胞色素c和caspase 9的相对表达倍数上调。目前的体外研究证实阿糖胞苷叶酸偶联壳聚糖纳米粒在MCF-7细胞中的细胞毒性有所改善。
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