Affiliation:
1. College of Chemistry and Pharmaceutical Sciences Qingdao Agricultural University Qingdao China
2. School of Medicine and Pharmacy Ocean University of China Qingdao China
3. Department of Central Laboratory Qilu Hospital (Qingdao), Cheeloo College of Medicine, Shandong University Qingdao China
4. Department of Public Course Teaching University of Health and Rehabilitation Sciences Qingdao China
Abstract
AbstractIntracellular zinc ion (Zn2+) accumulation disrupts the Zn2+ homeostasis, providing an ion‐overloading anticancer strategy with great potential. The self‐adaptation of tumor cells to ion concentration, however, puts forward higher requirements for the design of ion‐overloading strategy. Herein, “block and attack” antitumor strategy was applied through a composite nanomaterials (UHSsPZH NPs). The strategy demonstrated powerful ion interference ability through both “blocking” the efflux of excess Zn2+ via gene silencing and “attacking” tumor cells via target delivery of ZnO2. After cellular internalization, ZnO2 was degraded to Zn2+ and hydrogen peroxide (H2O2), and the gene expression of zinc transporter 1 (ZnT1) was silenced by targeting of released siRNA, which together caused intracellular Zn2+‐overload. Disorder of Zn2+ further interfered with intracellular Ca2+ homeostasis, inhibited the electron transport chain and promoted the production of endogenous reactive oxygen species (ROS), which assisted the “attack” to tumor cells together with the exogenous ROS generated by UHSsPZH NPs under 980 nm laser irradiation. In summary, this work supplies a “block and attack” strategy for the application of ion homeostasis interference in tumor therapy.
Funder
Natural Science Foundation of Shandong Province
National Natural Science Foundation of China
Youth Innovation Team Project for Talent Introduction and Cultivation in Universities of Shandong Province
Subject
General Medicine,General Chemistry
Cited by
5 articles.
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