喜树碱 (CPT) 是一种单萜吲哚生物碱，具有广谱抗癌活性。然而，其应用受到溶解性差、缺乏靶向特异性和严重副作用的阻碍。 CPT 的结构衍生化和开发合适的药物递送系统是解决这些问题的潜在策略。在这项研究中，我们发现来自智人的蛋白质细胞色素 P450 家族 1 亚家族 A 成员 1 (CYP1A1) 催化 CPT 产生 9-羟基喜树碱 (9-HCPT)，其水溶性和细胞毒性增加。然后，我们创建了一种基于 RNA-蛋白质复合物的药物递送系统，具有酶和 pH 响应性，并通过蛋白质模块组装提高了纳米药物的靶向性和稳定性。纳米颗粒的亚细胞定位可以使用荧光 RNA 探针进行可视化。我们的结果不仅鉴定了负责 CPT 结构衍生化以合成 9-HCPT 的蛋白质 CYP1A1，而且还提供了增强丝基药物递送系统在肿瘤治疗中的利用的潜在策略。版权所有 © 2024。由 Elsevier B.V. 出版。

Camptothecin (CPT) is a monoterpenoid indole alkaloid with a wide spectrum of anticancer activity. However, its application is hindered by poor solubility, lack of targeting specificity, and severe side effects. Structural derivatization of CPT and the development of suitable drug delivery systems are potential strategies for addressing these issues. In this study, we discovered that the protein Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) from Homo sapiens catalyzes CPT to yield 9-hydroxycamptothecin (9-HCPT), which exhibits increased water solubility and cytotoxicity. We then created a RNA-protein complex based drug delivery system with enzyme and pH responsiveness and improved the targeting and stability of the nanomedicine through protein module assembly. The subcellular localization of nanoparticles can be visualized using fluorescent RNA probes. Our results not only identified the protein CYP1A1 responsible for the structural derivatization of CPT to synthesize 9-HCPT but also offered potential strategies for enhancing the utilization of silk-based drug delivery systems in tumor therapy.Copyright © 2024. Published by Elsevier B.V.