College of Engineering and Applied Sciences, Nanjing University, Nanjing 210023, China.
Wuxi Xishan NJU Institute of Applied Biotechnology, Wuxi 214105, China.
ACS Appl Bio Mater. 2024 Sep 16;7(9):6055-6064. doi: 10.1021/acsabm.4c00681. Epub 2024 Sep 3.
Both boron neutron capture therapy (BNCT) and photothermal therapy (PTT) have been applied to tumor treatment in clinical. However, their therapeutic efficacy is limited. For BNCT, the agents not only exhibit poor targeting ability but also permit only a single irradiation session within a course due to significant radiation risks. In the context of PTT, despite enhanced selectivity, the limited photothermal effect fails to meet clinical demands. Hence, the imperative arises to combine these two therapies to enhance tumor-killing capabilities and improve the targeting of BNCT agents by leveraging the advantages of PTT agents. In this study, we synthesized a potential responsive agent by linking 4-mercaptophenylboronic acid (MPBA) and IR-780 dye that served as the agents for BNCT and PTT, respectively, which possesses the dual capabilities of photothermal effects and thermal neutron capture. Results from both in vitro and in vivo research demonstrated that IR780-MPBA effectively inhibits tumor growth through its photothermal effect with no significant toxicity. Furthermore, IR780-MPBA exhibited substantial accumulation in tumor tissues and superior tumor-targeting capabilities compared with MPBA, which demonstrated that IR780-MPBA possesses significant potential as a combined antitumor therapy of PTT and BNCT, presenting a promising approach for antitumor treatments.
硼中子俘获治疗(BNCT)和光热治疗(PTT)已在临床上应用于肿瘤治疗。然而,它们的治疗效果有限。对于 BNCT,由于存在严重的辐射风险,试剂不仅表现出较差的靶向能力,而且在一个疗程内只能进行单次照射。在 PTT 的情况下,尽管选择性增强,但有限的光热效应无法满足临床需求。因此,有必要将这两种疗法结合起来,通过利用 PTT 试剂的优势来增强肿瘤杀伤能力并提高 BNCT 试剂的靶向性。在这项研究中,我们通过连接 4-巯基苯硼酸(MPBA)和 IR-780 染料合成了一种潜在的响应性试剂,分别作为 BNCT 和 PTT 的试剂,具有光热效应和热中子俘获的双重能力。体外和体内研究的结果表明,IR780-MPBA 通过光热效应有效抑制肿瘤生长,没有明显的毒性。此外,与 MPBA 相比,IR780-MPBA 在肿瘤组织中具有显著的积累和优异的肿瘤靶向能力,这表明 IR780-MPBA 作为 PTT 和 BNCT 的联合抗肿瘤治疗具有重要潜力,为抗肿瘤治疗提供了一种有前途的方法。