Department of Orthopaedics, Shanghai Key Laboratory for Prevention and Treatment of Bone and Joint Diseases, Shanghai Institute of Traumatology and Orthopaedics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, P. R. China.
Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200233, P. R. China.
Adv Mater. 2022 Apr;34(15):e2110283. doi: 10.1002/adma.202110283. Epub 2022 Mar 7.
Deleterious effects to normal tissues and short biological half-life of sonosensitizers limit the applications of sonodynamic therapy (SDT). Herein, a new sonosensitizer (Cu(II)NS) is synthesized that consists of porphyrins, chelated Cu , and poly(ethylene glycol) (PEG) to overcome the challenges of SDT. As Cu contains 27 electrons, Cu(II)NS has an unpaired electron (open shell), resulting in a doublet ground state and little sonosensitivity. Overexpressed glutathione in the tumor can reduce Cu to generate Cu(I)NS, leading to a singlet ground state and recuperative sonosensitivity. Additionally, PEG endows Cu(II)NS with increased blood biological half-life and enhanced tumor accumulation, further increasing the effect of SDT. Through regulating the valence state of Cu, cancer SDT with enhanced therapeutic index is achieved.
声敏剂对正常组织的有害影响和较短的生物半衰期限制了声动力学疗法（SDT）的应用。在此，合成了一种新的声敏剂（Cu(II)NS），它由卟啉、螯合的 Cu 和聚乙二醇（PEG）组成，以克服 SDT 的挑战。由于 Cu 含有 27 个电子，Cu(II)NS 具有未配对的电子（开壳），导致基态为双重态，声敏性较小。肿瘤中过表达的谷胱甘肽可以还原 Cu 生成 Cu(I)NS，导致基态为单重态，恢复声敏性。此外，PEG 赋予 Cu(II)NS 增加的血液生物半衰期和增强的肿瘤积累，进一步增加 SDT 的效果。通过调节 Cu 的价态，实现了具有增强治疗指数的癌症 SDT。
