Nanoenabled Intracellular Calcium Bursting for Safe and Efficient Reversal of Drug Resistance in Tumor Cells.

【作者】 Junjie Liu, Chunyu Zhu, Lihua Xu, Danyu Wang, Wei Liu, Kaixiang Zhang*, Zhenzhong Zhang* , and Jinjin Shi*

【期刊名】 Nano Letters

【影响因子】 11.238

【作者单位】 School of Pharmaceutical Sciences, Zhengzhou University, 100 Kexue Avenue, Zhengzhou 450001, PR China

【年，卷(期)：页码】2020 doi.org/10.1021/acs.nanolett.0c03042

【关键词】 calcium ion nanogenerator intracellular Ca2+ bursting reversal of drug resistance calcium interference

【摘要】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.

【全文链接】https://pubs.acs.org/doi/full/10.1021/acs.nanolett.0c03042