Calcium Peroxide-Based Nanosystem with Cancer Microenvironment-Activated Capabilities for Imaging Guided Combination...

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, Ca²⁺ homeostasis is closely related to the normal function of mitochondria. By destroying the Ca²⁺ 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 Ca²⁺ retention and enrichment. We designed a targeted and tumor microenvironment (TME)-responsive CaO₂-based nanosystem that can selectively target cancer cells for pH-controlled degradation and drug release, alter cellular physiological mechanisms by disrupting Ca²⁺ homeostasis in an artificial manner, and introduce mitochondrial Ca²⁺ 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 H₂O₂ released from CaO₂ 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.