Photodynamic therapy (PDT) is often applied in a clinical setting to treat bladder cancer. However, current photosensitizers report drawbacks such as low efficacy, low selectivity, and numerous side effects, which have limited the clinical values of PDT for bladder cancer. Previously, we developed the first bladder cancer-specific aptamer that can selectively bind to and be internalized by bladder tumor cells versus normal uroepithelium cells. Here, we use an aptamer-based drug delivery system to deliver photosensitizer chlorine e6 (Ce6) into bladder tumor cells. In addition to Ce6, we also incorporate catalase into the drug complex to increase local oxygen levels in the tumor tissue. Compared with free Ce6, an aptamer-guided DNA nanotrain (NT) loaded with Ce6 and catalase (NT–Catalase–Ce6) can specifically recognize bladder cancer cells, produce oxygen locally, induce ROS in tumor cells, and cause mitochondrial apoptosis. In an orthotopic mouse model of bladder cancer, the intravesical instillation of NT–Catalase–Ce6 exhibits faster drug internalization and a longer drug retention time in tumor tissue compared with that in normal urothelium. Moreover, our modified PDT significantly inhibits tumor growth with fewer side effects such as cystitis than free Ce6. This aptamer-based photosensitizer delivery system can therefore improve the selectivity and efficacy and reduce the side effects of PDT treatment in mouse models of bladder cancer, bearing a great translational value for bladder cancer intravesical therapy.

中文翻译：

---

通过肿瘤特异性适体靶向递送过氧化氢酶和光敏剂 Ce6 可有效对抗体内膀胱癌

光动力疗法（PDT）经常应用于临床治疗膀胱癌。然而，目前的光敏剂存在功效低、选择性低、副作用多等缺点，限制了PDT治疗膀胱癌的临床价值。此前，我们开发了第一个膀胱癌特异性适体，与正常尿路上皮细胞相比，它可以选择性地结合膀胱肿瘤细胞并被膀胱肿瘤细胞内化。在这里，我们使用基于适体的药物递送系统将光敏剂氯 e6 (Ce6) 递送到膀胱肿瘤细胞中。除了 Ce6 之外，我们还将过氧化氢酶加入到药物复合物中，以增加肿瘤组织中的局部氧水平。与游离Ce6相比，负载Ce6和过氧化氢酶（NT-Catalase-Ce6）的适体引导的DNA纳米链（NT）可以特异性识别膀胱癌细胞，局部产生氧气，诱导肿瘤细胞内ROS，并引起线粒体凋亡。在膀胱癌原位小鼠模型中，与正常尿路上皮相比，NT-过氧化氢酶-Ce6的膀胱内滴注在肿瘤组织中表现出更快的药物内化和更长的药物保留时间。此外，与游离 Ce6 相比，我们改良的 PDT 显着抑制肿瘤生长，且膀胱炎等副作用更少。因此，这种基于适配体的光敏剂递送系统可以提高膀胱癌小鼠模型中PDT治疗的选择性和疗效，并减少副作用，对膀胱癌膀胱内治疗具有巨大的转化价值。