Zhang Zhuo, Yue Xu, Lan Ni, Zhang Yongkang, Li Zesen, Jin Fangzhou, Wang Yifei, Guan Bai-Ou, Ran Yang, Liu Kaisheng
Guangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Shenzhen People's Hospital, The Second Clinical Medical College, Jinan University, Shenzhen 518020, China.
Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China.
ACS Appl Mater Interfaces. 2025 Jan 22;17(3):4368-4379. doi: 10.1021/acsami.4c11734. Epub 2024 Oct 30.
Effective treatment of malignant tumors remains a thorny issue in current medicine. As a new type of anticancer strategy, photothermal therapy (PTT) has attracted tremendous attention due to its favorable therapeutic effectiveness, high spatial-temporal controllability, and low occurrence of side effects. However, the efficacy of PTT is significantly reduced due to the limited penetration of light and heat-induced overexpression of heat shock protein (Hsp). Herein, we propose an antitumor synergistic therapy that combines fiber-optic PTT and Hsp inhibitors. A rare-earth-doped optical fiber was used as the PTT actuator, and the Hsp inhibitor AT533 was loaded on the fiber surface by use of a hydrogel layer. PTT fibers can be guided to reach tumor lesions directly without being subject to the light penetration limit. The Hsp inhibitor can be released upon the softening of the hydrogel layer under photoheating to deactivate Hsp in the tumor and thus reduce the resistance of the tumor to PTT. This synergistic treatment enhanced the effect of PTT and successfully eradicated tumors in colorectal cancer (CRC) xenograft mouse models, providing a feasible way to realize antitumor and antirecurrence treatment. More importantly, the success of the synergistic treatment of PTT and Hsp inhibition opens new avenues for the development of multimodal and multitype synergistic fiber-optic treatments, which offer pronounced enhancement of therapeutic effectiveness for treating cancer.
恶性肿瘤的有效治疗仍是当前医学中的一个棘手问题。作为一种新型抗癌策略，光热疗法（PTT）因其良好的治疗效果、高时空可控性和低副作用发生率而备受关注。然而，由于光穿透受限以及热诱导热休克蛋白（Hsp）过表达，PTT的疗效显著降低。在此，我们提出一种将光纤PTT与Hsp抑制剂相结合的抗肿瘤协同疗法。一种稀土掺杂光纤用作PTT致动器，通过水凝胶层将Hsp抑制剂AT533负载在光纤表面。PTT光纤可被引导直接到达肿瘤病灶，而不受光穿透限制。在光热作用下水凝胶层软化时，Hsp抑制剂可释放出来，使肿瘤中的Hsp失活，从而降低肿瘤对PTT的抗性。这种协同治疗增强了PTT的效果，并在结直肠癌（CRC）异种移植小鼠模型中成功根除肿瘤，为实现抗肿瘤和抗复发治疗提供了一种可行方法。更重要的是，PTT与Hsp抑制协同治疗的成功为多模式、多类型协同光纤治疗的发展开辟了新途径，显著提高了癌症治疗的疗效。
