National Council of Research-Institute of Clinical Physiology, Pisa 56124, Italy.
Division of Experimental Oncology, Urological Research Institute (URI), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan 20132, Italy.
Proc Natl Acad Sci U S A. 2024 Sep 10;121(37):e2411583121. doi: 10.1073/pnas.2411583121. Epub 2024 Sep 5.
Residual nonvisible bladder cancer after proper treatment caused by technological and therapeutic limitations is responsible for tumor relapse and progression. This study aimed to demonstrate the feasibility of a solution for simultaneous detection and treatment of bladder cancer lesions smaller than one millimeter. The α5β1 integrin was identified as a specific marker in 81% of human high-grade nonmuscle invasive bladder cancers and used as a target for the delivery of targeted gold nanorods (GNRs). In a preclinical model of orthotopic bladder cancer expressing the α5β1 integrin, the photoacoustic imaging of targeted GNRs visualized lesions smaller than one millimeter, and their irradiation with continuous laser was used to induce GNR-assisted hyperthermia. Necrosis of the tumor mass, improved survival, and computational modeling were applied to demonstrate the efficacy and safety of this solution. Our study highlights the potential of the GNR-assisted theranostic strategy as a complementary solution in clinical practice to reduce the risk of nonvisible residual bladder cancer after current treatment. Further validation through clinical studies will support the findings of the present study.
经过适当治疗后仍存在的肉眼不可见膀胱癌是导致肿瘤复发和进展的原因，这是由技术和治疗的局限性造成的。本研究旨在证明一种能够同时检测和治疗小于一毫米膀胱癌病变的解决方案的可行性。α5β1 整联蛋白在 81%的人类高级别非肌肉浸润性膀胱癌中被鉴定为特异性标志物，并被用作靶向金纳米棒（GNRs）的递药靶点。在表达α5β1 整联蛋白的原位膀胱癌临床前模型中，靶向 GNRs 的光声成像是可视化小至一毫米的病变，并用连续激光照射它们以诱导 GNR 辅助的热疗。肿瘤坏死、提高存活率和计算模型的应用证明了这种解决方案的疗效和安全性。我们的研究强调了 GNR 辅助治疗策略作为临床实践中一种补充解决方案的潜力，以降低当前治疗后肉眼不可见的膀胱癌残留风险。通过临床研究的进一步验证将支持本研究的发现。
