College of Chemistry, Henan Joint International Research Laboratory of Green Construction of Functional Molecules and Their Bioanalytical Applications, Zhengzhou University, Zhengzhou 450001, P. R. China.
Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.
Theranostics. 2024 Aug 19;14(13):5141-5151. doi: 10.7150/thno.96136. eCollection 2024.
One of the main challenges in chemotherapy is achieving high treatment efficacy while minimizing adverse events. Fully exploiting the therapeutic potential of an old drug and monitoring its effects is highly valuable, but often difficult to achieve. In this study, by encapsulating disulfiram (DSF) approved by US Food and Drug Administration, semiconducting polymer nanocomplex (MEHPPV), and Chlorin e6 into a polymeric matrix F127 via nanoprecipitation method, a nanosystem (FCMC) was developed for afterglow imaging guided cancer treatment. The characteristics, stability as well as the ability of singlet oxygen (O) production of FCMC were first carefully examined. Then, we studied the mechanism for enhanced anti-cancer efficiency and afterglow luminescence . For experiments , 4T1 subcutaneous xenograft tumor mice were injected with FCMC via the tail vein every three days and the antitumor effect of FCMC was evaluated by monitoring tumor volume and body weight every three day. The nanosystem, which combines DSF with Ce6, can generates abundant O that enhances the antitumor activity of DSF. The results show that FCMC-treated group exhibits an obviously higher tumor-growth inhibition rate of 67.89% after 15 days of treatment, compared to the control group of F127@MEHPPV-CuET. Moreover, Ce6 also greatly enhances the afterglow luminescence intensity of MEHPPV and promotes the redshift of the afterglow emission towards the ideal near-infrared imaging window, thereby enabling efficient afterglow tumor imaging . This multifunctional nanoplatform not only improves the anticancer efficacy of DSF, but also enables monitoring tumor via robust afterglow imaging, thus exhibiting great potential for cancer therapy and early therapeutic outcome prediction.
化疗面临的主要挑战之一是在尽量减少不良反应的情况下实现高治疗效果。充分挖掘一种老药的治疗潜力并监测其效果具有重要价值,但通常难以实现。在这项研究中,通过将美国食品和药物管理局批准的二硫化硒(DSF)、半导体聚合物纳米复合物(MEHPPV)和叶绿素 e6 包裹在聚合物基质 F127 中,通过纳米沉淀法制备了一种纳米系统(FCMC),用于余晖成像引导癌症治疗。首先仔细研究了 FCMC 的特性、稳定性以及单线态氧(O)生成能力。然后,我们研究了增强抗癌效率和余晖发光的机制。对于实验,通过尾静脉每三天向 4T1 皮下异种移植肿瘤小鼠注射一次 FCMC,并通过每三天监测肿瘤体积和体重来评估 FCMC 的抗肿瘤效果。该纳米系统将 DSF 与 Ce6 结合,可产生丰富的 O,从而增强 DSF 的抗肿瘤活性。结果表明,在治疗 15 天后,与 F127@MEHPPV-CuET 的对照组相比,FCMC 处理组的肿瘤生长抑制率明显更高,为 67.89%。此外,Ce6 还大大增强了 MEEPPV 的余晖发光强度,并促使余晖发射向理想的近红外成像窗口红移,从而实现高效的余晖肿瘤成像。这种多功能纳米平台不仅提高了 DSF 的抗癌效果,还能够通过强大的余晖成像监测肿瘤,因此在癌症治疗和早期治疗效果预测方面具有巨大的潜力。