GSH-responsive sequential mitochondria-targeting nanoagents for photothermal-enhanced chemodynamic therapy

Materials & Design

Chunhua Lu¹  Yihang Ding²  Jiajia Yang³  Yuhong Lin⁴  Huaming He⁵  Fang Zhao⁵  Xiankun Tu⁵  Wukun Zhong⁵  Yuling Yang⁵ 

[1] Corresponding authors.;Department of Neurosurgery, Fujian Medical University Union Hospital, Neurosurgical Institute of Fujian Province, Fuzhou 350001, PR China;Department of Ultrasound, Fujian Medical University Union Hospital, Fuzhou 350001, PR China;Institute of Nanobiomaterials and Immunology, School of Life Science, Taizhou University, Taizhou 318000, PR China;MOE Key Laboratory for Analytical Science of Food Safety and Biology, Fujian Provincial Key Laboratory of Analysis and Detection Technology for Food Safety, State Key Laboratory of Photocatalysis on Energy and Environment, Col-lege of Chemistry, Fuzhou University, Fuzhou 350116, PR China;

关键词: Mitochondrial targeted;    Photothermal therapy (PTT);    Chemodynamic therapy (CDT);    Drug delivery;   

DOI  :  

来源: DOAJ

【 摘 要 】

Mitochondria-targeting nanoparticles have proven to be promising platforms for cancer therapy. However, precise mitochondria targeting in the complex tumor environment is still challenging and requires more ingenious design. Herein, we developed the glutathione (GSH)-responsive nanoagents to target mitochondria in tumor cells precisely for photothermal-enhanced chemodynamic therapy (CDT). The nanoagents were designed by preparing the cubic shape of CuFeS2 nanoparticles that sequentially modified with mitochondrial-targeting peptide (KLAK) and integrin-targeting peptide (RGD), which KLAK and RGD were covalently conjugated via a disulfide bond. After being endocytosed into integrin-overexpressed tumor cells, disulfide bond was broken and RGD was separated from the nanoagents in the presence of overexpressed GSH. Then, the exposure of KLAK on the surface further aid the rustling nanoagents to target mitochondria. Under NIR laser irradiation, the surrounding temperature of the nanoagents would rise due to their excellent photothermal effect, resulting in the improvement of the Fenton reaction from the CuFeS2. It was well demonstrated that this photothermal-enhanced chemodynamic therapy nanoplatform could effectively damage the mitochondrial function and further induce the apoptosis of tumor cells. As a therapeutic platform with both tumor/mitochondria-targeting and PTT-enhanced CDT, our study has provided a new path in the field of cancer therapy.

【 授权许可】

Unknown