Salvioni Lucia, Testa Filippo, Barbieri Linda, Giustra Marco, Bertolini Jessica Armida, Tomaino Giulia, Tortora Paolo, Prosperi Davide, Colombo Miriam
Department of Biotechnology and Bioscience, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milano, Italy.
Pharmaceutics. 2022 Jul 21;14(7):1517. doi: 10.3390/pharmaceutics14071517.
Ribosome-inactivating proteins, including Saporin toxin, have found application in the search for innovative alternative cancer therapies to conventional chemo- and radiotherapy. Saporin's main mechanism of action involves the inhibition of cytoplasmic protein synthesis. Its strong theoretical efficacy is counterbalanced by negligible cell uptake and diffusion into the cytosol. In this work, we demonstrate that by immobilizing Saporin on iron oxide nanoparticles coated with an amphiphilic polymer, which promotes nanoconjugate endosomal escape, a strong cytotoxic effect mediated by ribosomal functional inactivation can be achieved. Cancer cell death was mediated by apoptosis dependent on nanoparticle concentration but independent of surface ligand density. The cytotoxic activity of Saporin-conjugated colloidal nanoparticles proved to be selective against three different cancer cell lines in comparison with healthy fibroblasts.
核糖体失活蛋白，包括皂草素毒素，已在寻找替代传统化疗和放疗的创新癌症疗法中得到应用。皂草素的主要作用机制涉及抑制细胞质蛋白质合成。其强大的理论疗效因细胞摄取和扩散到细胞质中的量可忽略不计而被抵消。在这项工作中，我们证明，通过将皂草素固定在涂有两亲聚合物的氧化铁纳米颗粒上，这种聚合物可促进纳米缀合物从内涵体逃逸，从而可实现由核糖体功能失活介导的强大细胞毒性作用。癌细胞死亡是由凋亡介导的，其依赖于纳米颗粒浓度，但与表面配体密度无关。与健康成纤维细胞相比，皂草素缀合的胶体纳米颗粒的细胞毒性活性被证明对三种不同的癌细胞系具有选择性。
