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评估依托泊苷透明质酸靶向固体脂质纳米粒对SK-OV-3细胞的细胞毒性

Evaluating Cytotoxicity of Hyaluronate Targeted Solid Lipid Nanoparticles of Etoposide on SK-OV-3 Cells.

作者信息

Mohammadi Ghalaei Parviz, Varshosaz Jaleh, Sadeghi Aliabadi Hojatollah

机构信息

Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, P.O. Box 81745-359, Isfahan 81746-73461, Iran.

Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran.

出版信息

J Drug Deliv. 2014;2014:746325. doi: 10.1155/2014/746325. Epub 2014 Apr 24.

Abstract

The epithelial ovarian carcinoma is one of the most fatal gynecological cancers. Etoposide is used in treating platinum-resistant ovarian cancer. Sodium hyaluronate is a substance that binds to the CD44 receptors overexpressed in SK-OV-3 cells of epithelial ovarian carcinoma. The aim of the present work was to study the cytotoxicity effect of hyaluronate targeted solid lipid nanoparticles (SLNs) of etoposide on SK-OV-3 cells. The cytotoxicity of the targeted and nontargeted SLNs of etoposide was compared to free drug on the SK-OV-3 cells by MTT assay method. The cellular uptake of the targeted and nontargeted nanoparticles containing sodium fluorescein was also studied. The difference of cell vitality between nontargeted nanoparticles and also targeted nanoparticles with free drug was significant. Targeted nanoparticles also caused more toxicity than nontargeted nanoparticles (P < 0.05). After 4 hours of incubating, the fluorescence was remarkably higher in the cells treated by targeted SLNs rather than nontargeted ones, and there was no observable fluorescence in cells incubated with pure sodium fluorescein. Hyaluronate targeted SLNs containing etoposide increased the cytotoxicity of etoposide on SK-OV-3 cells which may be a worthwhile potential method for reducing the prescribed dose and systemic side effects of this drug in epithelial ovarian carcinoma.

摘要

上皮性卵巢癌是最致命的妇科癌症之一。依托泊苷用于治疗铂耐药性卵巢癌。透明质酸钠是一种能与上皮性卵巢癌SK-OV-3细胞中过表达的CD44受体结合的物质。本研究的目的是研究依托泊苷的透明质酸靶向固体脂质纳米粒(SLNs)对SK-OV-3细胞的细胞毒性作用。通过MTT法比较了依托泊苷靶向和非靶向SLNs与游离药物对SK-OV-3细胞的细胞毒性。还研究了含有荧光素钠的靶向和非靶向纳米粒的细胞摄取情况。非靶向纳米粒与游离药物的靶向纳米粒之间的细胞活力差异显著。靶向纳米粒也比非靶向纳米粒具有更高的毒性(P < 0.05)。孵育4小时后,靶向SLNs处理的细胞中的荧光明显高于非靶向SLNs处理的细胞,而用纯荧光素钠孵育的细胞中未观察到荧光。含有依托泊苷的透明质酸靶向SLNs增加了依托泊苷对SK-OV-3细胞的细胞毒性,这可能是一种在减少该药物在上皮性卵巢癌中的规定剂量和全身副作用方面值得尝试的潜在方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1393/4020396/e902343bdaa2/JDD2014-746325.001.jpg

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