Background: A phthalimide-functionalized heptamethine cyanine dye, named Ph790H, is used for targeted photothermal cancer therapy in vivo. We highlight that the chemical structure of Ph790H is newly designed and synthesized for the first time in this study. Objectives: By possessing a rigid chloro-cyclohexenyl ring in the heptamethine cyanine backbone, the bifunctional near-infrared (NIR) fluorescent dye Ph790H can be preferentially accumulated in tumor without the need for additional targeting ligands, which is defined as the “structure-inherent tumor targeting” concept. Methods: The phototherapeutic effect of Ph790H is evaluated in HT-29 human colorectal cancer xenografts to be used as a cancer-targeting photothermal agent. Results: The results reveal that the Ph790H shows enhanced tumor accumulation in HT-29 xenografts 48 h post-injection with a high tumor-to-background ratio. After determination of the optimal timing for photothermal therapy (PTT), the HT-29 tumor-possessing nude mice pretreated with Ph790H are subsequently irradiated with an 808 nm NIR laser for 5 min. The tumor-targeted PTT treatment can efficiently inhibit the tumor development compared with that of control groups. Moreover, no tumor regrowth or Ph790H-induced mortality occurs after the treatment of Ph790H and laser irradiation during a period of monitoring. Conclusions: Therefore, this work demonstrates that the bifunctional phototheranostic agent Ph790H can be utilized for targeted cancer imaging and fluorescence-guided phototherapy simultaneously.
背景：本研究首次设计并合成了一种新型酞酰亚胺功能化七甲川花菁染料Ph790H，用于体内靶向光热癌症治疗。其化学结构具有创新性。目的：通过在七甲川花菁骨架中引入刚性氯代环己烯环，双功能近红外荧光染料Ph790H无需额外靶向配体即可在肿瘤部位优先富集，这体现了"结构固有肿瘤靶向"的设计理念。方法：以HT-29人结直肠癌异种移植瘤为模型，评估Ph790H作为癌症靶向光热剂的光治疗效果。结果：注射48小时后，Ph790H在HT-29移植瘤中表现出增强的肿瘤蓄积能力，具有较高的肿瘤背景比。确定最佳光热治疗时机后，对经Ph790H预处理的荷瘤裸鼠进行808 nm近红外激光照射5分钟。与对照组相比，这种肿瘤靶向光热治疗能有效抑制肿瘤发展。在监测期间，未观察到肿瘤再生或Ph790H诱导的死亡事件。结论：本研究表明双功能光诊疗剂Ph790H可同时实现靶向癌症成像和荧光引导的光疗。
A Phthalimide-Functionalized Heptamethine Cyanine Dye for Tumor-Targeted Photothermal Therapy
肿瘤(癌症)患者之家