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聚乙二醇(PEG)修饰伊立替康阳离子脂质体提高乳腺癌动物模型的治疗效果。

PEG-coated irinotecan cationic liposomes improve the therapeutic efficacy of breast cancer in animals.

机构信息

Department of Pharmaceutics, School of Pharmaceutical Sciences, Hebei Medical University, Research Center of Chinese Medicine Injection in Hebei Province, Shijiazhuang, China.

出版信息

Eur Rev Med Pharmacol Sci. 2013 Dec;17(24):3347-61.

Abstract

BACKGROUND

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females owing.

AIM

This study aimed to construct a kind of PEG-coated irinotecan cationic liposomes for investigating its efficacy and mechanism of action in the treatment of breast cancer in preclinical models.

MATERIALS AND METHODS

Evaluations were performed on the MDA-MB231 breast cancer cells, the xenografted MDA-MB231 cancer cells in Female nude mice and Sprague-Dawley (SD) rat. The liposomes were characterized through assays of cytotoxicity, intracellular uptake, nuclei morphology, antitumor activities, pharmacokinetics and tissue distribution.

RESULTS

The zeta potential of PEG-coated irinotecan cationic liposomes was approximately 23 mV. The PEG-coated irinotecan cationic liposomes were approximately 66nm in diameter, significantly increased the intracellular uptake of irinotecan, and showed strong inhibitory effect on MDA-MB231 breast cancer cells. A significant antitumor efficacy in the xenografted MDA-MB231 breast cancer cells in nude mice was evidenced by intravenous administration of PEG-coated irinotecan cationic liposomes. PEG-coated irinotecan cationic liposomes also improved the irinotecan blood circulation time and showed an enhanced drug concentration in tumor.

CONCLUSIONS

PEG-coated irinotecan cationic liposomes had significant inhibitory effect against breast cancer in vitro and in vivo, hence providing a new strategy for treating breast cancer.

摘要

背景

乳腺癌是女性中最常见的癌症,也是癌症死亡的主要原因。

目的

本研究旨在构建一种聚乙二醇(PEG)修饰的伊立替康阳离子脂质体,以研究其在乳腺癌临床前模型中的疗效和作用机制。

材料与方法

在 MDA-MB231 乳腺癌细胞、裸鼠异种移植 MDA-MB231 肿瘤细胞和 Sprague-Dawley(SD)大鼠中进行了评价。通过细胞毒性、细胞内摄取、细胞核形态、抗肿瘤活性、药代动力学和组织分布等实验对脂质体进行了评估。

结果

PEG 修饰的伊立替康阳离子脂质体的zeta 电位约为 23 mV。PEG 修饰的伊立替康阳离子脂质体的直径约为 66nm,显著增加了伊立替康的细胞内摄取,并对 MDA-MB231 乳腺癌细胞表现出强烈的抑制作用。静脉注射 PEG 修饰的伊立替康阳离子脂质体在裸鼠异种移植 MDA-MB231 乳腺癌细胞中表现出显著的抗肿瘤疗效。PEG 修饰的伊立替康阳离子脂质体还延长了伊立替康的血液循环时间,并在肿瘤中显示出增强的药物浓度。

结论

PEG 修饰的伊立替康阳离子脂质体对乳腺癌具有显著的体内外抑制作用,为治疗乳腺癌提供了一种新策略。

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