Among anticancer nanomedicines, squalenoyl nanocomposites have obtained encouraging outcomes in a great variety of tumors. The prodrug squalenoyl-gemcitabine has been chosen in this study to construct a novel multidrug nanosystem in combination with edelfosine, an alkyl-lysophopholipid with proven anticancer activity. Given their amphiphilic nature, it was hypothesized that both anticancer compounds, with complementary molecular targets, could lead to the formation of a new multitherapy nanomedicine. Nanoassemblies were formulated by the nanoprecipitation method and characterized by dynamic light scattering, transmission electron microscopy and X-ray photoelectron spectroscopy. Because free edelfosine is highly hemolytic, hemolysis experiments were performed using human blood erythrocytes and nanoassemblies efficacy was evaluated in a patient-derived metastatic pediatric osteosarcoma cell line. It was observed that these molecules spontaneously self-assembled as stable and monodisperse nanoassemblies of 51 ± 1 nm in a surfactant/polymer free-aqueous suspension. Compared to squalenoyl-gemcitabine nanoassemblies, the combination of squalenoyl-gemcitabine with edelfosine resulted in smaller particle size and a new supramolecular conformation, with higher stability and drug content, and ameliorated antitumor profile.

在抗癌纳米药物中，角鲨烯酰基纳米复合物已在多种肿瘤中获得令人鼓舞的结果。在这项研究中，选择了前药角鲨烯酰基吉西他滨与依德福星（一种具有被证实的抗癌活性的烷基溶石脂）相结合，构建了一个新型的多药纳米系统。考虑到它们的两亲性质，可以假设这两种具有互补分子靶标的抗癌化合物都可以导致新的多疗法纳米药物的形成。通过纳米沉淀法制备纳米组件，并通过动态光散射，透射电子显微镜和X射线光电子能谱进行表征。由于游离的依德福星具有很高的溶血性，使用人血红细胞进行溶血实验，并在患者来源的转移性小儿骨肉瘤细胞系中评估了纳米组装的功效。观察到这些分子在表面活性剂/聚合物无水悬浮液中自发自组装为51±1 nm的稳定且单分散的纳米组件。与角鲨烯基-吉西他滨纳米组件相比，角鲨烯基-吉西他滨与依德福星的组合产生更小的粒径和新的超分子构象，具有更高的稳定性和药物含量，并改善了抗肿瘤特性。