In vitro assessment of liposomal neridronate on MDA-MB-231 human breast cancer cells
In vitro assessment of liposomal neridronate on MDA-MB-231 human breast cancer cells
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DOI：
10.1016/j.ijpharm.2009.09.011
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发表时间：
2010-01-04
影响因子：
5.8
通讯作者：
Seksek, Olivier
中科院分区：
文献类型：
--
作者：
Chebbi, Imene;Migianu-Griffoni, Evelyne;Seksek, Olivier
几十年来，双磷酸盐一直用于骨相关疾病的标准治疗，包括各种恶性肿瘤的骨转移，而且它们对早期癌细胞本身也可能有毒。为了更好地递送奈立膦酸盐（一种活性相对较差的含氮双膦酸盐），在癌细胞系（MDA-MB-231、U87-MG 和 Caco2）上对脂质体进行了体外评估。化学合成后，这种水溶性分子被封装到含有 DOPC:DOPG:Chol（72:27:1 摩尔比）的脂质体中。使用MTT方法以及细胞迁移和侵袭试验评估奈立膦酸（游离或脂质体）对治疗后细胞活力或增殖的影响；这些技术显示奈立膦酸对 MDA-MB-231 细胞的作用显着改善，当奈立膦酸被封装时，EC50 降低了 50 倍。通过流式细胞术和荧光显微镜观察脂质体的内化，证明通过内吞途径进行内化。此外，由于基质金属蛋白酶（特别是 MMP-2 和 MMP-9）的过度表达与许多癌症类型的不良预后相关，因此 MMP 表达的检测是治疗效率的令人满意的指标，然后在治疗的细胞上进行。在 MDA-MB-231 细胞上，奈立膦酸盐包埋在脂质体中时，MPP 表达也显着降低。 (C) 2009 Elsevier B.V. 保留所有权利。
Bisphosphonates have been used for decades in the standard therapy of bone-related diseases, including bone metastasis of various malignancies, and they might as well be toxic on early cancer cells themselves. In order to allow a better delivery of neridronate (a N-containing bisphosphonate with relatively poor activity), liposomes were evaluated in vitro on cancer cell lines (MDA-MB-231, U87-MG and Caco2). After chemical synthesis, this water-soluble molecule was encapsulated into liposomes containing DOPC:DOPG:Chol (72:27:1 molar ratio). The influence of neridronate (free or liposomal) on cell viability or proliferation after treatment was evaluated using the MTT method, as well as cell migration and invasion assays; these techniques showed a drastic improvement of the action of neridronate on MDA-MB-231 cells with an EC50 50 times lower when neridronate was encapsulated. Internalization of liposomes was followed by flow cytometry and fluorescence microscopy, demonstrating internalization via the endocytic pathway. Furthermore, since overexpression of matrix metalloproteinases (particularly MMP-2 and MMP-9) has been correlated to poor prognosis in many cancer types, detection of MMP expression is a satisfactory indication of the therapy efficiency and was then performed on treated cells. On MDA-MB-231 cells, MPPs expression was also significantly reduced by neridronate while entrapped in liposomes. (C) 2009 Elsevier B.V. All rights reserved.