Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Road, Chongqing 400038, China.
Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, 30 Gaotanyan Road, Chongqing 400038, China.
Biomaterials. 2014 Apr;35(13):4116-24. doi: 10.1016/j.biomaterials.2014.01.061. Epub 2014 Feb 12.
Personalized oncology significantly relies on the development of theranostic agents to integrate cancer therapeutics and diagnostics. Current strategy for development of such multifunctional agents requires multistep chemical conjugation with cancer specific ligands, contrast agents and therapeutic drugs. In this study, we reported a near infrared (NIR) heptamethine indocyanine dye, IR-780, which selectively accumulated in the mitochondria of drug-resistant human lung cancer cells (A549/DR) and significantly inhibited cell growth, self-renewal and migration without the need of any chemical conjugation. IR-780 was also able to induce A549/DR cell apoptosis by disrupting the mitochondrial function. Furthermore, IR-780 dye exhibited remarkable tumoricidal activity and inhibited tumor recurrence in mouse syngeneic Lewis lung carcinoma xenograft model. With the unique properties of targeting, near infrared imaging and inhibitive effect to the drug-resistant cancer cells both in vitro and in vivo, IR-780 may represent a potential theranostic agent for tumor recurrence.
个体化肿瘤学在很大程度上依赖于治疗诊断一体化试剂的发展，以整合癌症治疗和诊断。目前开发此类多功能试剂的策略需要用癌症特异性配体、对比剂和治疗药物进行多步化学偶联。在这项研究中，我们报道了一种近红外（NIR）七甲川吲哚菁染料 IR-780，它选择性地积聚在耐药性人肺癌细胞（A549/DR）的线粒体中，并且无需任何化学偶联即可显著抑制细胞生长、自我更新和迁移。IR-780 还通过破坏线粒体功能诱导 A549/DR 细胞凋亡。此外，IR-780 染料在小鼠同源性 Lewis 肺癌异种移植模型中表现出显著的杀瘤活性，并抑制肿瘤复发。IR-780 具有靶向、近红外成像以及在体外和体内抑制耐药癌细胞的独特特性，可能代表一种用于肿瘤复发的治疗诊断一体化试剂。
