Human serum albumin is playing an increasing role as a drug carrier in clinical settings. Biotin molecules are often used as suitable tags in targeted anti-tumor drug delivery systems. We report on the synthesis and properties of a new multimodal theranostic conjugate based on an anti-cancer fluorinated nucleotide conjugated with a biotinylated dual-labeled albumin. Interestingly, in vitro and in vivo study revealed stronger anti-tumor activity of the non-tagged theranostic conjugate than that of the biotin-tagged conjugate, which can be explained by decreased binding of the biotin-tagged conjugate to cellular receptors. Our study sheds light on the importance of site-specific albumin modification for the design of albumin-based drugs with desirable pharmaceutical properties.

人血清白蛋白在临床环境中作为药物载体发挥着越来越重要的作用。生物素分子通常被用作靶向抗肿瘤药物递送系统中的合适标签。我们报告了基于抗癌的氟化核苷酸与生物素化的双标记白蛋白偶联的新型多峰治疗药物偶联物的合成和性质。有趣的是，体外和体内研究显示，未标记的治疗药物缀合物比抗生物素标记的缀合物具有更强的抗肿瘤活性，这可以通过降低抗生物素标记的缀合物与细胞受体的结合来解释。我们的研究揭示了位点特异性白蛋白修饰在设计具有所需药物特性的基于白蛋白的药物方面的重要性。