非肌层浸润性膀胱癌（NMIBC）的不完全切除会增加疾病复发的风险。分子探针成像引导手术是减轻术后复发的关键策略。传统的光学分子探针主要由针对肿瘤细胞的抗体/肽和荧光基团组成，受到NMIBC细胞的高度异质性的挑战，导致探针灵敏度不足。我们开发了一种胶原蛋白粘附探针（CA-P）来靶向肿瘤微环境中的胶原蛋白，旨在解决成像灵敏度不足的问题。探索胶原蛋白在动物膀胱癌模型和人类膀胱癌组织中的分布特征。验证了CA-P的合成和性能。在动物模型中，测试了 CA-P 的成像性能，并与我们之前报道的近红外探针 PLSWT7-DMI 进行了比较。使用人离体膀胱组织评估CA-P的临床转化潜力。肿瘤细胞表面的胶原蛋白分布与其在正常尿路上皮中的表达不同。体外研究表明，CA-P 在与胶原蛋白相互作用时能够经历“溶胶-凝胶”转变。在动物模型和人类离体膀胱标本中，CA-P 与 PLSWT7-DMI 相比表现出卓越的成像性能。该探针的灵敏度为94.1%，特异性为81%。CA-P具有克服肿瘤细胞异质性和增强成像灵敏度的能力，在临床前模型中表现出良好的成像结果。这些发现为 CA-P 在 NMIBC 术中导航中的应用提供了理论基础。© 2024。作者获得 Springer-Verlag GmbH 德国（Springer Nature 旗下公司）的独家许可。

The incomplete resection of non-muscle invasive bladder cancer (NMIBC) augments the risk of disease recurrence. Imaging-guided surgery by molecular probes represents a pivotal strategy for mitigating postoperative recurrence. Traditional optical molecular probes, primarily composed of antibodies/peptides targeting tumour cells and fluorescent groups, are challenged by the high heterogeneity of NMIBC cells, leading to inadequate probe sensitivity. We have developed a collagen-adhesive probe (CA-P) to target the collagen within the tumour microenvironment, aiming to address the issue of insufficient imaging sensitivity.The distribution characteristics of collagen in animal bladder cancer models and human bladder cancer tissues were explored. The synthesis and properties of CA-P were validated. In animal models, the imaging performance of CA-P was tested and compared with our previously reported near-infrared probe PLSWT7-DMI. The clinical translational potential of CA-P was assessed using human ex vivo bladder tissues.The distribution of collagen on the surface of tumour cells is distinct from its expression in normal urothelium. In vitro studies have demonstrated the ability of the CA-P to undergo a "sol-gel" transition upon interaction with collagen. In animal models and human ex vivo bladder specimens, CA-P exhibits superior imaging performance compared to PLSWT7-DMI. The sensitivity of this probe is 94.1%, with a specificity of 81%.CA-P demonstrates the capability to overcome tumour cell heterogeneity and enhance imaging sensitivity, exhibiting favorable imaging outcomes in preclinical models. These findings provide a theoretical basis for the application of CA-P in intraoperative navigation for NMIBC.© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.