Department of Pharmaceutics, School of Pharmaceutical Sciences, Hebei Medical University, Research Center of Chinese Medicine Injection in Hebei Province, Shijiazhuang, China.
Eur Rev Med Pharmacol Sci. 2013 Dec;17(24):3347-61.
Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females owing.
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.
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.
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.
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.
乳腺癌是女性中最常见的癌症,也是癌症死亡的主要原因。
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。
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。
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。
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。