Mesbahi Nooshin, Yoon Hosog, Fulton Melody D, Berkman Clifford E
Washington State University, Department of Chemistry Pullman, WA 99164-4630, United States.
Washington State University, Department of Chemistry Pullman, WA 99164-4630, United States.
Bioorg Med Chem Lett. 2025 Jul 1;122:130213. doi: 10.1016/j.bmcl.2025.130213. Epub 2025 Mar 28.
We developed pretargeting approach for the targeted delivery of molecular payloads to prostate cancer cells expressing the hallmark enzyme-biomarker, prostate-specific membrane antigen (PSMA). We employed a phosphoramidate-based PSMA ligand (CTT1298) with a click-ready DBCO group for strain-promoted azide-alkyne cycloaddition (SPAAC) and used 6-FAM-Azide as a model payload. PSMA+ cells were treated with a fluorescent PSMA-targeted probe (FAM-C6-1298), confirming delivery and accumulation. Further, live-cell experiments with DBCO-C6-1298 and 5-FAM-azide demonstrated selective pretargeted delivery. These results validate the feasibility of this pretargeting strategy in PSMA+ cells, suggesting its potential for preclinical applications with therapeutic and diagnostic payloads, enhancing the specificity and safety of prostate cancer treatments.
我们开发了一种预靶向方法，用于将分子载荷靶向递送至表达标志性酶生物标志物前列腺特异性膜抗原（PSMA）的前列腺癌细胞。我们使用了一种基于氨基磷酸酯的PSMA配体（CTT1298），其带有用于应变促进的叠氮化物-炔烃环加成（SPAAC）的点击就绪型二苯并环辛炔（DBCO）基团，并使用6-羧基荧光素叠氮化物作为模型载荷。用荧光PSMA靶向探针（FAM-C6-1298）处理PSMA+细胞，证实了递送和积累。此外，用DBCO-C6-1298和5-羧基荧光素叠氮化物进行的活细胞实验证明了选择性预靶向递送。这些结果验证了这种预靶向策略在PSMA+细胞中的可行性，表明其在携带治疗和诊断载荷的临床前应用中的潜力，可提高前列腺癌治疗的特异性和安全性。
