Nanoenabled Intracellular Calcium Bursting for Safe and Efficient Reversal of Drug Resistance in Tumor CellsClick to copy article linkArticle link copied!
- Junjie LiuJunjie LiuSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaKey Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province, China, Zhengzhou University, Zhengzhou 450001, ChinaCollaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, China, Zhengzhou University, Zhengzhou 450001, ChinaMore by Junjie Liu
- Chunyu ZhuChunyu ZhuSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaMore by Chunyu Zhu
- Lihua XuLihua XuSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaMore by Lihua Xu
- Danyu WangDanyu WangSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaMore by Danyu Wang
- Wei LiuWei LiuSchool of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaKey Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province, China, Zhengzhou University, Zhengzhou 450001, ChinaCollaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, China, Zhengzhou University, Zhengzhou 450001, ChinaMore by Wei Liu
- Kaixiang Zhang*Kaixiang Zhang*Email: [email protected]. (K.Z.)School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaKey Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province, China, Zhengzhou University, Zhengzhou 450001, ChinaCollaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, China, Zhengzhou University, Zhengzhou 450001, ChinaMore by Kaixiang Zhang
- Zhenzhong Zhang*Zhenzhong Zhang*Email: [email protected]. (Z.Z.)School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaKey Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province, China, Zhengzhou University, Zhengzhou 450001, ChinaCollaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, China, Zhengzhou University, Zhengzhou 450001, ChinaMore by Zhenzhong Zhang
- Jinjin Shi*Jinjin Shi*Email: [email protected]. (J.S.)School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, ChinaKey Laboratory of Targeting Therapy and Diagnosis for Critical Diseases, Henan Province, China, Zhengzhou University, Zhengzhou 450001, ChinaCollaborative Innovation Center of New Drug Research and Safety Evaluation, Henan Province, Zhengzhou, China, Zhengzhou University, Zhengzhou 450001, ChinaMore by Jinjin Shi
Abstract

Multidrug resistance (MDR) of a tumor is the main cause of failure of clinical chemotherapy. Herein, we report a simple, yet versatile, tumor-targeting “calcium ion nanogenerator” (TCaNG) to reverse drug resistance by inducing intracellular Ca2+ bursting. Consequently, the TCaNG could induce Ca2+ bursting in acidic lysosomes of tumor cells and then reverse drug resistance according to the following mechanisms: (i) Ca2+ specifically accumulates in mitochondria, suppressing cellular respiration and relieving tumor hypoxia, thus inhibiting P-glycoprotein biosynthesis by downregulating HIF-1α expression. (ii) Ca2+-bursting-induced respiratory depression blocks intracellular ATP production, which further leads to the P-gp incompetence. As a result, the TCaNG could decrease the IC50 of DOX to MCF-7/ADR cells by approximately 30 times and reduce the proliferation of drug-resistant tumors by approximately 13 times without obvious side effects. This simple, safe, and effective “Ca2+ bursting” strategy holds the potential for clinical application in tumor treatment.
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