School of Chemistry and Chemical Engineering, Frontiers Science Center for Transformative Molecules, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, China.
Department of Oral & Maxillofacial-Head & Neck Oncology, Shanghai Key Laboratory of Stomatology Cosmetic Laser Center, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
Biomater Sci. 2023 Apr 11;11(8):2809-2817. doi: 10.1039/d3bm00007a.
Specific cancer diagnosis at an early stage plays a significant role in preventing cancer metastasis and reducing cancer mortality. Thus, exploring specific and sensitive fluorescent probes to realize early cancer diagnosis is an urgent need in clinic. Aminopeptidase N (APN/CD13), overexpressed in numerous malignant tumors, is an important tumor biomarker associated with cancer progression, invasion, and metastasis. In this study, a novel fluorescent molecule APN-SUB, capable of monitoring APN in real time, is encapsulated in a pH-responsive block copolymer (termed APN-SUB nanoprobe) for cancer diagnosis. APN-SUB contains a fluorophore center and a trigger moiety (leucine group), which is covalently conjugated on the fluorophore with an amide bond. The hydrolysis of the amide bond in APN-SUB activated by APN leads to a red shift of maximum fluorescence emission wavelength from 495 nm to 600 nm, realizing dual-color transformation from green to red. Moreover, the APN-SUB nanoprobe with pH-responsiveness is prepared to improve the accumulation and the release rate in the tumor region. It is worth noting that the APN-SUB nanoprobe exhibits good performance for APN imaging, namely, superior limit of detection (0.14 nU mL), excellent selectivity and strong photostability. More importantly, the APN-SUB nanoprobe can be successfully employed as a color-convertible fluorescent probe for cancer diagnosis by tracking the activity of APN with high specificity and sensitivity , demonstrating its potential value for cancer diagnosis.
早期明确癌症诊断对于预防癌症转移和降低癌症死亡率具有重要意义。因此，探索特异性强、灵敏度高的荧光探针实现早期癌症诊断是临床的迫切需求。天冬酰胺肽酶 N（APN/CD13）在多种恶性肿瘤中过表达，是与癌症进展、侵袭和转移相关的重要肿瘤标志物。本研究构建了一种新型荧光分子 APN-SUB，该分子可实时监测 APN，将其包载于 pH 响应型嵌段共聚物中（命名为 APN-SUB 纳米探针）用于癌症诊断。APN-SUB 含有荧光团中心和触发基团（亮氨酸基团），两者通过酰胺键共价连接在荧光团上。APN 激活 APN-SUB 中的酰胺键水解，导致最大荧光发射波长从 495nm 红移至 600nm，实现了从绿色到红色的双色转变。此外，还制备了具有 pH 响应性的 APN-SUB 纳米探针以提高在肿瘤区域的积累和释放速率。值得注意的是，APN-SUB 纳米探针在 APN 成像方面表现出优异的性能，即检测限低（0.14nU mL）、选择性好、光稳定性强。更重要的是，APN-SUB 纳米探针可以成功用作具有高特异性和灵敏度的可转换颜色的荧光探针用于癌症诊断，证明了其在癌症诊断中的潜在价值。
