A Dual Heat Shock Protein Down-Regulation Strategy Using PDA/Cu/ICG/R Controlled by NIR "Switch" Enhances Mild-Photothermal Therapy Effect

被引:22
作者
Ding, Xin [1 ,2 ]
Wang, Tianyu [3 ]
Bai, Shiwei [4 ]
Yang, Mian [1 ,2 ]
Peng, Na [1 ,2 ,5 ]
Qiu, Tao [3 ]
Liu, Yi [1 ,2 ,6 ]
机构
[1] Wuhan Univ Sci & Technol, Key Lab Coal Convers & New Carbon Mat Hubei Prov, Coll Chem & Chem Engn, Wuhan 430081, Peoples R China
[2] Wuhan Univ Sci & Technol, Inst Adv Mat & Nanotechnol, Coll Chem & Chem Engn, Wuhan 430081, Peoples R China
[3] Wuhan Univ, Dept Organ Transplantat, Renmin Hosp, Wuhan 430060, Peoples R China
[4] Chinese Acad Sci, Beijing Natl Lab Mol Sci BNLMS, CAS Key Lab Colloid Interface & Chem Thermodynam, Inst Chem, Beijing 100190, Peoples R China
[5] Huazhong Univ Sci & Technol, Belt & Rd Joint Lab Measurement & Control Technol, Wuhan 430074, Hubei, Peoples R China
[6] Wuhan Polytech Univ, Sch Chem & Environm Engn, Wuhan 430023, Peoples R China
基金
中国国家自然科学基金;
关键词
adenosine triphosphate; heat shock proteins; mild photothermal therapy; polydopamine; NANOPARTICLES; DEGRADATION;
D O I
10.1002/adhm.202300929
中图分类号
R318 [生物医学工程];
学科分类号
0831 ;
摘要
The purpose of this study is to down-regulate heat shock proteins and improve the mild photothermal therapy (mild-PTT) effect of polydopamine (PDA) by preparing the nanosystem of Cu2+ and indocyanine green (ICG)-loaded PDA nanospheres with surface modification of integrin-targeted cyclic peptide (cRGD) (PDA/Cu/ICG/R), which can limit ATP synthesis through the double mitochondrial destruction pathway. In vitro and in vivo experiments using PDA/Cu/ICG/R irradiated with an NIR laser demonstrate that when NIR is "OFF," Cu2+ can undergo Fenton-like reaction in tumor cells, producing a large amount of hydroxyl radicals (center dot OH), which leads to oxidative stress in cells. This oxidative stress can cause mitochondrial oxidative phosphorylation dysfunction, resulting in limited ATP synthesis. When NIR is "ON," mild-PTT can accelerate Cu2+ to produce center dot OH. Simultaneously, NIR can activate ICG to produce reactive oxygen species (ROS) storm, amplify intracellular oxidative stress, and continuously damage mitochondria. The biodegradability of PDA greatly reduces the risk of toxicity caused by long-term retention of PDA/Cu/ICG/R in organisms. Finally, the improvement of the mild-PTT effect of PDA is successfully achieved through the double mitochondrial destruction pathway of Cu2+ and ICG controlled by NIR "switch."
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页数:16
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