ATP Suppression by pH-Activated Mitochondria-Targeted Delivery of Nitric Oxide Nanoplatform for Drug Resistance Reversal and Metastasis Inhibition
Yongyan Deng
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027 P. R. China
Search for more papers by this authorFan Jia
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027 P. R. China
Search for more papers by this authorXiaohui Chen
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027 P. R. China
Search for more papers by this authorCorresponding Author
Qiao Jin
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027 P. R. China
E-mail: [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Jian Ji
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027 P. R. China
E-mail: [email protected], [email protected]
Search for more papers by this authorYongyan Deng
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027 P. R. China
Search for more papers by this authorFan Jia
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027 P. R. China
Search for more papers by this authorXiaohui Chen
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027 P. R. China
Search for more papers by this authorCorresponding Author
Qiao Jin
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027 P. R. China
E-mail: [email protected], [email protected]
Search for more papers by this authorCorresponding Author
Jian Ji
MOE Key Laboratory of Macromolecule Synthesis and Functionalization of Ministry of Education, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou, Zhejiang, 310027 P. R. China
E-mail: [email protected], [email protected]
Search for more papers by this authorAbstract
Mitochondria, which are important mediators for cancer initiation, growth, metastasis, and drug resistance, have been considered as a major target in cancer therapy. Herein, an acid-activated mitochondria-targeted drug nanocarrier is constructed for precise delivery of nitric oxide (NO) as an adenosine triphosphate (ATP) suppressor to amplify the therapeutic efficacy in cancer treatments. By combining α-cyclodextrin (α-CD) and acid-cleavable dimethylmaleic anhydride modified PEG conjugated mitochondria-targeting peptide, the nanocarrier shows prolonged blood circulation time and enhanced cellular uptake together with selectively restoring mitochondria-targeting capability under tumor extracellular pH (6.5). Such specific mitochondria-targeted delivery of NO proves crucial in inducing mitochondria dysfunction through facilitating mitochondrial membrane permeabilization and downregulating ATP level, which can inhibit P-glycoprotein-related bioactivities and formation of tumor-derived microvesicles to combat drug resistance and cancer metastasis. Therefore, this pioneering acid-activated mitochondria-targeted NO nanocarrier is supposed to be a malignant tumor opponent and may provide insights for diverse NO-relevant cancer treatments.
Conflict of Interest
The authors declare no conflict of interest.
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