Sobot Dunja, Mura Simona, Rouquette Marie, Vukosavljevic Branko, Cayre Fanny, Buchy Eric, Pieters Grégory, Garcia-Argote Sébastien, Windbergs Maike, Desmaële Didier, Couvreur Patrick
Institut Galien Paris-Sud, UMR 8612, CNRS, University Paris-Sud, Université Paris-Saclay, Faculté de Pharmacie, 5 rue Jean-Baptiste Clément, 92296 Châtenay-Malabry Cedex, France.
Department of Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland, Helmholtz Center for Infection Research, Campus E8 1, 66123 Saarbruecken, Germany.
Mol Ther. 2017 Jul 5;25(7):1596-1605. doi: 10.1016/j.ymthe.2017.05.016. Epub 2017 Jun 9.
Selective delivery of anticancer drugs to rapidly growing cancer cells can be achieved by taking advantage of their high receptor-mediated uptake of low-density lipoproteins (LDLs). Indeed, we have recently discovered that nanoparticles made of the squalene derivative of the anticancer agent gemcitabine (SQGem) strongly interacted with the LDLs in the human blood. In the present study, we showed both in vitro and in vivo that such interaction led to the preferential accumulation of SQGem in cancer cells (MDA-MB-231) with high LDL receptor expression. As a result, an improved pharmacological activity has been observed in MDA-MB-231 tumor-bearing mice, an experimental model with a low sensitivity to gemcitabine. Accordingly, we proved that the use of squalene moieties not only induced the gemcitabine insertion into lipoproteins, but that it could also be exploited to indirectly target cancer cells in vivo.
通过利用快速生长的癌细胞对低密度脂蛋白（LDL）的高受体介导摄取，可以实现抗癌药物向这些细胞的选择性递送。事实上，我们最近发现，由抗癌药物吉西他滨的角鲨烯衍生物（SQGem）制成的纳米颗粒与人血液中的LDL强烈相互作用。在本研究中，我们在体外和体内均表明，这种相互作用导致SQGem在具有高LDL受体表达的癌细胞（MDA-MB-231）中优先积累。结果，在对吉西他滨敏感性较低的实验模型——携带MDA-MB-231肿瘤的小鼠中观察到了改善的药理活性。因此，我们证明，使用角鲨烯部分不仅能诱导吉西他滨插入脂蛋白，还可用于在体内间接靶向癌细胞。
