Open-Shell Nanosensitizers for Glutathione Responsive Cancer Sonodynamic Therapy

被引:97
|
作者
Wang, Han [1 ]
Guo, Jinxiao [2 ]
Lin, Wilson [3 ,4 ]
Fu, Zi [1 ]
Ji, Xiuru [1 ]
Yu, Bo [3 ,4 ]
Lu, Min [1 ]
Cui, Wenguo [1 ]
Deng, Lianfu [1 ]
Engle, Jonathan W. [3 ,4 ]
Wu, Zhiyuan [5 ]
Cai, Weibo [3 ,4 ]
Ni, Dalong [1 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med,Ruijin Hosp, Dept Orthopaed,Shanghai Inst Traumatol & Orthopae, Shanghai Key Lab Prevent & Treatment Bone & Joint, Shanghai 200025, Peoples R China
[2] Shanghai Jiao Tong Univ, Shanghai Jiao Tong Univ Affiliated Peoples Hosp 6, Dept Orthopaed, Shanghai 200233, Peoples R China
[3] Univ Wisconsin, Dept Radiol, Madison, WI 53705 USA
[4] Univ Wisconsin, Dept Med Phys, Madison, WI 53705 USA
[5] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Intervent Radiol, Shanghai 200025, Peoples R China
基金
中国博士后科学基金; 中国国家自然科学基金; 美国国家卫生研究院;
关键词
glutathione response; nanomedicine; open shell; positron emission tomography imaging; sonodynamic therapy;
D O I
10.1002/adma.202110283
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
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.
引用
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页数:8
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