Liu Yadong, Lv Huiyan, Chen Yaodong, Ye Shazhou, Zheng Zhong, Chen Lei, Yan Zejun, Li Xingyi
Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People's Republic of China.
State Key Laboratory of Ultrasound in Medicine and Engineering, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People's Republic of China.
Int J Nanomedicine. 2025 Sep 1;20:10701-10719. doi: 10.2147/IJN.S534840. eCollection 2025.
Due to the complex structure and variable microenvironment in the progression of bladder cancer, the efficacy of traditional treatment methods such as surgery and chemotherapy is limited. Tumor residual, recurrence and metastasis are still difficult to treat. The integration of diagnosis and treatment based on nanoparticles can offer the potential for precise tumor localization and real-time therapeutic monitoring. Photodynamic therapy (PDT), which generates reactive oxygen species (ROS) under laser irradiation, can be effectively combined with photothermal therapy (PTT) and chemodynamic therapy (CDT) to target non-muscle-invasive bladder tumors. In this study, Cu(OH)PO@PAA nanoparticles with photoacoustic (PA) imaging capabilities were utilized to explore their potential for precise intraoperative tumor identification and multimodal therapy.
The generation of ROS was detected to evaluate the potential of PDT and copper ion-induced CDT. Additionally, the PA imaging capability and biosafety of the nanoparticles were systematically evaluated. Finally, the anti-tumor efficacy of Cu(OH)PO@PAA-mediated CDT/PDT/PTT and the underlying mechanisms were assessed in vitro and in vivo.
Cu(OH)PO@PAA could implement the CDT effect through a Cu-induced Fenton-like reaction and substantial consumption of glutathione (GSH). Besides, Cu(OH)PO@PAA could execute NIR-I-triggered PDT by generating O and thermal images showed that Cu(OH)PO@PAA has the potential to perform PTT through light-heat energy conversion. Cu(OH)PO@PAA possessed dose-dependent PA signal transduction ability. Without laser exposure, Cu(OH)PO@PAA weakened cell viability, induced apoptosis, and suppressed epithelial-mesenchymal transition (EMT) by exhibiting the CDT effect alone. However, after the introduction of PDT and/or PTT, the above anti-tumor effects were significantly enhanced.
This study systematically explores the combined anti-cancer mechanisms from the perspective of epithelial-mesenchymal transition, providing a theoretical and technical foundation for bladder cancer treatment.
由于膀胱癌进展过程中结构复杂且微环境多变，手术和化疗等传统治疗方法的疗效有限。肿瘤残留、复发和转移仍然难以治疗。基于纳米颗粒的诊断与治疗一体化可为肿瘤精确定位和实时治疗监测提供可能。光动力疗法（PDT）在激光照射下产生活性氧（ROS），可与光热疗法（PTT）和化学动力疗法（CDT）有效结合，用于靶向非肌层浸润性膀胱肿瘤。在本研究中，利用具有光声（PA）成像能力的Cu(OH)PO@PAA纳米颗粒来探索其在术中精确肿瘤识别和多模态治疗方面的潜力。
检测ROS的产生以评估PDT和铜离子诱导的CDT的潜力。此外，系统评估了纳米颗粒的PA成像能力和生物安全性。最后，在体外和体内评估了Cu(OH)PO@PAA介导的CDT/PDT/PTT的抗肿瘤疗效及其潜在机制。
Cu(OH)PO@PAA可通过铜诱导的类芬顿反应和大量消耗谷胱甘肽（GSH）实现CDT效应。此外，Cu(OH)PO@PAA可通过产生单线态氧执行近红外I触发的PDT，热成像显示Cu(OH)PO@PAA具有通过光热能量转换进行PTT的潜力。Cu(OH)PO@PAA具有剂量依赖性的PA信号转导能力。在无激光照射的情况下，Cu(OH)PO@PAA仅通过展现CDT效应就可削弱细胞活力、诱导细胞凋亡并抑制上皮-间质转化（EMT）。然而，引入PDT和/或PTT后，上述抗肿瘤作用显著增强。
本研究从上皮-间质转化的角度系统探索了联合抗癌机制，为膀胱癌治疗提供了理论和技术基础。
