PDF(Pubmed)
Abstract：
Chemo and siRNA synergic treatments for tumors is a promising new therapeutic trend. Selenocystine, a selenium analog of cysteine, has been considered a potential antitumor agent due to its redox perturbing role. In this study, we developed a nanocarrier for siRNA based on a selenocystine analog engineered polyetherimide and achieved traceable siRNA delivery and the synergic killing of tumor cells. Notably, we applied the label-free Schiff base fluorescence mechanism, which enabled us to trace the siRNA delivery and to monitor the selenocystine analogs\' local performance. A novel selenocystine-derived fluorescent Schiff base linker was used to crosslink the polyetherimide, thereby generating a traceable siRNA delivery vehicle with green fluorescence. Moreover, we found that this compound induced tumor cells to undergo senescence. Together with the delivery of a siRNA targeting the anti-apoptotic BCL-xl/w genes in senescent cells, it achieved a synergistic inhibition function by inducing both senescence and apoptosis of tumor cells. Therefore, this study provides insights into the development of label-free probes, prodrugs, and materials towards the synergic strategies for cancer therapy.
摘要：
化疗和siRNA协同治疗肿瘤是一个有前途的新的治疗趋势。硒半胱氨酸,半胱氨酸的硒类似物，由于其氧化还原干扰作用，已被认为是潜在的抗肿瘤剂。在这项研究中,我们开发了一种基于硒代半胱氨酸类似物工程聚醚酰亚胺的siRNA纳米载体，并实现了可追溯的siRNA递送和对肿瘤细胞的协同杀伤。值得注意的是,我们应用无标记希夫碱荧光机制，这使我们能够追踪siRNA的递送并监测硒代半胱氨酸类似物的局部表现。一种新颖的硒代半胱氨酸衍生的荧光席夫碱接头用于交联聚醚酰亚胺，从而产生具有绿色荧光的可追踪的siRNA递送载体。此外，我们发现这种化合物诱导肿瘤细胞衰老。与在衰老细胞中递送靶向抗凋亡BCL-xl/w基因的siRNA一起，它通过诱导肿瘤细胞衰老和凋亡实现协同抑制功能。因此,这项研究提供了对无标记探针发展的见解，前药,以及癌症治疗协同策略的材料。
