Porto Vanesa, Borrajo Erea, Buceta David, Carneiro Carmen, Huseyinova Shahana, Domínguez Blanca, Borgman Kyra J E, Lakadamyali Melike, Garcia-Parajo Maria F, Neissa José, García-Caballero Tomás, Barone Giampaolo, Blanco M Carmen, Busto Natalia, García Begoña, Leal José Maria, Blanco José, Rivas José, López-Quintela M Arturo, Domínguez Fernando
Department of Physiology and Centro de Investigaciones en Medicina Molecular y Enfermedades Crónicas (CIMUS), IDIS, Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain.
Departments of Physical Chemistry and Applied Physics, Nanomag Laboratory, IIT, Universidade de Santiago de Compostela, 15782, Santiago de Compostela, Spain.
Adv Mater. 2018 Jul 3:e1801317. doi: 10.1002/adma.201801317.
Nanomaterials with very low atomicity deserve consideration as potential pharmacological agents owing to their very small size and to their properties that can be precisely tuned with minor modifications to their size. Here, it is shown that silver clusters of three atoms (Ag -AQCs)-developed by an ad hoc method-augment chromatin accessibility. This effect only occurs during DNA replication. Coadministration of Ag -AQCs increases the cytotoxic effect of DNA-acting drugs on human lung carcinoma cells. In mice with orthotopic lung tumors, the coadministration of Ag -AQCs increases the amount of cisplatin (CDDP) bound to the tumor DNA by fivefold without modifying CDDP levels in normal tissues. As a result, CDDP coadministered with Ag -AQCs more strongly reduces the tumor burden. Evidence of the significance of targeting chromatin compaction to increase the therapeutic index of chemotherapy is now provided.
由于原子数极低的纳米材料尺寸非常小且其性质可通过对尺寸进行微小修饰而精确调控，因此值得作为潜在的药物制剂加以考虑。在此，研究表明通过一种特殊方法制备的三原子银簇（Ag -AQCs）可增强染色质可及性。这种效应仅在DNA复制过程中出现。联合施用Ag -AQCs可增强作用于DNA的药物对人肺癌细胞的细胞毒性作用。在原位肺肿瘤小鼠中，联合施用Ag -AQCs可使与肿瘤DNA结合的顺铂（CDDP）量增加五倍，而不改变正常组织中的CDDP水平。结果，与Ag -AQCs联合施用的CDDP能更有效地减轻肿瘤负担。现在有证据表明，靶向染色质压缩以提高化疗治疗指数具有重要意义。
