Calcium Peroxide-Based Nanosystem with Cancer Microenvironment-Activated Capabilities for Imaging Guided Combination Therapy via Mitochondrial Ca 2+ Overload and Chemotherapy

作者：Qianqian Sun, Bin Liu, Ruoxi Zhao, Lili Feng, Zhao Wang, Shuming Dong, Yushan Dong, Shili Gai, He Ding, Piaoping Yang · 发表于：ACS Applied Materials & Interfaces · 年份：2021 · DOI：10.1021/acsami.1c13304 · 被引用次数：65 · 研究领域：Nanoplatforms for cancer theranostics、Advanced Nanomaterials in Catalysis、Luminescence Properties of Advanced Materials

Mitochondria are the “power plant” of the cell, providing a constant source of energy, and are involved in a variety of intracellular signaling pathways. Among these pathways, Ca 2+ homeostasis is closely related to the normal function of mitochondria. By destroying the Ca 2+ steady state of mitochondria and disrupting their multiple cellular activities, tumor cell killing can be achieved. In addition, the presence of an intracellular oxidative stress state triggers the closure of cellular calcium channels, which leads to intracellular Ca 2+ retention and enrichment. We designed a targeted and tumor microenvironment (TME)-responsive CaO 2 -based nanosystem that can selectively target cancer cells for pH-controlled degradation and drug release, alter cellular physiological mechanisms by disrupting Ca 2+ homeostasis in an artificial manner, and introduce mitochondrial Ca 2+ excess-mediated apoptosis. Meanwhile, the production of Ca(OH) 2 will raise the pH of the microenvironment and subsequently promote the oxidation process of glutathione by H 2 O 2 released from CaO 2 degradation, achieving the goal of remodeling TME. Moreover, calcium overload of tumor cells and calcification of tissues can both inhibit tumor growth and act as a contrast agent for computed tomography imaging.