State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China.
University of Science and Technology of China, Hefei 230026, P. R. China.
Biomater Sci. 2021 Oct 26;9(21):7115-7123. doi: 10.1039/d1bm01154e.
The clinical application of conventional chemotherapeutic agents, represented by cisplatin, is limited by severe side effects. So, it is essential to explore more safer and controlled drug delivery systems for synergistic chemotherapy. In this work, we designed dual-sensitive dual-prodrug nanoparticles (DDNPs) for photoactivated platinum-based synergistic chemotherapy. With photosensitivity, DDNPs could be photoactivated from inert Pt(IV) to toxic Pt(II) under safe UVA light in a spatiotemporally controlled manner. Concurrently, mild could be generated from DDNPs to assist the endo/lysosomal escape of DDNPs for better photoactivated chemotherapy (PACT). Furthermore, with acid-sensitivity, demethylcantharidin (DMC), a protein phosphatase 2A (PP2A) inhibitor, was released to block the DNA repair pathway and thereby could sensitize platinum-based chemotherapy in intracellular acidic microenvironments. Along with a precise ratio (Pt : DMC = 1 : 2), DDNPs had a powerful synergistic anti-cancer effect and . In the future, DDNPs have great potential as a safe and multifunctional drug delivery system for precise nanomedicine in clinical treatments.
传统化疗药物（以顺铂为代表）的临床应用受到严重副作用的限制。因此，探索更安全、更可控的药物传递系统以实现协同化疗至关重要。在这项工作中，我们设计了用于光激活基于铂的协同化疗的双敏感双前药纳米粒子（DDNPs）。通过光敏感性，DDNPs 可以在安全的 UVA 光下以时空控制的方式从惰性的 Pt(IV)光激活为有毒的 Pt(II)。同时，温和的可以从 DDNPs 中产生，以帮助 DDNPs 的内体/溶酶体逃逸，从而实现更好的光激活化疗（PACT）。此外，由于具有酸敏感性，去甲基斑蝥素（DMC），一种蛋白磷酸酶 2A（PP2A）抑制剂，被释放以阻断 DNA 修复途径，从而可以在细胞内酸性微环境中增强基于铂的化疗的敏感性。在精确的比例（Pt：DMC = 1：2）下，DDNPs 具有强大的协同抗癌作用，。在未来，DDNPs 有望成为一种安全、多功能的药物传递系统，用于临床治疗中的精确纳米医学。
