Uveal melanoma (UM) is an intraocular tumor which is almost lethal at the metastatic stage due to the lack of effective treatments. In this regard, we have developed an albumin-based nanostructure (ABN) containing AZD8055 (ABN-AZD), which is a potent mTOR kinase inhibitor, for its efficient delivery to the tumors. The drug has been conjugated to ABN using tailored linkers that have a disulfide moiety, allowing its release selectively and effectively in the presence of an elevated concentration of glutathione, such as inside the tumoral cells. Our therapeutic approach induced significant cellular toxicity in uveal melanoma cells, but not in non-tumoral keratinocytes, highlighting the excellent selectivity of the system. In addition, these nanostructures showed excellent activity in vivo, decreasing the tumor surface compared to the free AZD8055 in mice models. Remarkably, the results obtained were achieved employing a dose 23 times lower than those used in previous reports.

葡萄膜黑色素瘤（UM）是一种眼内肿瘤，由于缺乏有效的治疗方法，在转移阶段几乎是致命的。在这方面，我们开发了一种含有 AZD8055 (ABN-AZD) 的基于白蛋白的纳米结构 (ABN)，它是一种有效的 mTOR 激酶抑制剂，可有效递送至肿瘤。该药物已使用具有二硫键部分的定制接头与 ABN 缀合，使其在谷胱甘肽浓度升高的情况下（例如在肿瘤细胞内）选择性且有效地释放。我们的治疗方法在葡萄膜黑色素瘤细胞中诱导了显着的细胞毒性，但在非肿瘤角质形成细胞中没有，突出了该系统的优异选择性。此外，这些纳米结构在体内表现出优异的活性，与小鼠模型中的游离 AZD8055 相比，减少了肿瘤表面。值得注意的是，所获得的结果是使用比以前报告中使用的剂量低 23 倍的剂量实现的。