Open-Shell Nanosensitizers for Glutathione Responsive Cancer Sonodynamic Therapy

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 Cu2+, and poly(ethylene glycol) (PEG) to overcome the challenges of SDT. As Cu2+ 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 Cu2+ 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.

Automated summary

In this study, a new sonosensitizer Cu(II)NS was synthesized to overcome the challenges of sonodynamic therapy (SDT). By including porphyrins, chelated Cu2+, and poly(ethylene glycol) (PEG), Cu(II)NS showed improved therapeutic effects. The overexpressed glutathione in the tumor can reduce Cu2+ to generate Cu(I)NS, leading to enhanced sonosensitivity. Moreover, PEG increased the blood biological half-life and tumor accumulation of Cu(II)NS, further enhancing the effect of SDT.