早期检测和切除患者的膀胱癌对于预防肿瘤复发和进展至关重要。由于当前的成像技术可能无法检测到原位癌的小病变，患者在初次诊断后往往会复发，因此需要频繁的随访和治疗。为了获得一种对膀胱癌敏感且高分辨率的成像模式，我们开发了一种基于PEG修饰金纳米棒（GNRs）作为对比剂的光声成像方法，并且使用经功能化的肽循环[CphgisoDGRG]（Iso4），一种选择性结合α5β1整合素的膀胱癌细胞配体。称之为GNRs@PEG-Iso4的产物通过两步简单的方法制备，该方法基于GNRs和硫辛酸-聚乙二醇(PEG-5KDa)-马来酰亚胺的激活以及使用肽Iso4的功能化。生化和生物学研究表明，GNRs@PEG-Iso4能够有效识别纯化的α5β1整合素和α5β1阳性的膀胱癌细胞。GNRs@PEG-Iso4稳定，不会在尿液或5%氯化钠中聚集，也不会在冻结/解冻循环或长时间暴露在55 °C后沉淀，而且更重要的是，注入膀胱后不会沉淀。将GNRs@PEG-Iso4导入携带正交MB49-Luc膀胱肿瘤的小鼠膀胱内，随后进行光声成像，能够有效检测到小的癌症病变。与肿瘤病变的结合能够被中和抗-α5β1整合素抗体竞争；此外，对健康的膀胱（α5β1阴性）观察到没有结合。GNRs@PEG-Iso4代表了一种简单而稳定的光声成像对比剂，可以用于诊断小的膀胱癌病变。 © 2023年。BioMed Central 有限公司，Springer Nature 的一部分。

Early detection and removal of bladder cancer in patients is crucial to prevent tumor recurrence and progression. Because current imaging techniques may fail to detect small lesions of in situ carcinomas, patients with bladder cancer often relapse after initial diagnosis, thereby requiring frequent follow-up and treatments.In an attempt to obtain a sensitive and high-resolution imaging modality for bladder cancer, we have developed a photoacoustic imaging approach based on the use of PEGylated gold nanorods (GNRs) as a contrast agent, functionalized with the peptide cyclic [CphgisoDGRG] (Iso4), a selective ligand of α5β1 integrin expressed by bladder cancer cells. This product (called GNRs@PEG-Iso4) was produced by a simple two-step procedure based on GNRs activation with lipoic acid-polyethyleneglycol(PEG-5KDa)-maleimide and functionalization with peptide Iso4. Biochemical and biological studies showed that GNRs@PEG-Iso4 can efficiently recognize purified integrin α5β1 and α5β1-positive bladder cancer cells. GNRs@PEG-Iso4 was stable and did not aggregate in urine or in 5% sodium chloride, or after freeze/thaw cycles or prolonged exposure to 55 °C, and, even more importantly, do not settle after instillation into the bladder. Intravesical instillation of GNRs@PEG-Iso4 into mice bearing orthotopic MB49-Luc bladder tumors, followed by photoacoustic imaging, efficiently detected small cancer lesions. The binding to tumor lesions was competed by a neutralizing anti-α5β1 integrin antibody; furthermore, no binding was observed to healthy bladders (α5β1-negative), pointing to a specific targeting mechanism.GNRs@PEG-Iso4 represents a simple and robust contrast agent for photoacoustic imaging and diagnosis of small bladder cancer lesions.© 2023. BioMed Central Ltd., part of Springer Nature.