Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, United States.
Department of Chemistry, Rice University, 6100 Main Street, Houston, TX 77005, United States; Department of Biosciences, Rice University, 6100 Main Street, Houston, TX 77005, United States; Department of Bioengineering, Rice University, 6100 Main Street, Houston, TX 77005, United States.
Bioorg Med Chem Lett. 2023 Jul 15;91:129365. doi: 10.1016/j.bmcl.2023.129365. Epub 2023 Jun 7.
The use of light to activate prodrugs offers a promising method for the precise control of drug release, reducing drug-related side effects, and enhancing therapeutic effectiveness. We have created a novel prodrug system that utilizes a unique, heavy-atom-free photosensitizer to produce singlet oxygen, which then triggers the conversion of the prodrug into its active form. This system has been successfully demonstrated through the creation of "photo-unclick" prodrugs of paclitaxel (PTX), combretastatin A-4 (CA-4), and 10-hydroxy-7-ethylcamptothecin (SN-38). These prodrugs show decreased toxicity in the absence of light, but exhibit increased toxicity when exposed to red light.
利用光来激活前药为药物释放的精确控制提供了一种很有前途的方法，可以减少与药物相关的副作用，并提高治疗效果。我们创建了一种新型前药系统，该系统利用独特的、不含重原子的光敏剂来产生单线态氧，然后触发前药转化为其活性形式。通过创建紫杉醇（PTX）、康普瑞汀 A-4（CA-4）和 10-羟基喜树碱（SN-38）的“光点击”前药，成功地证明了该系统的有效性。这些前药在没有光照的情况下毒性降低，但在暴露于红光下时毒性增加。
