Abstract

The development of stimuli-responsive nanoplatform provides powerful tool for simultaneously enhancing the efficiency and accuracy of cancer therapies. Herein, we develop a pH-programmed responsive and synergistically theranostic nanoplatform based on CaCO 3 mineralized single atom iron nanoparticles (SAF NPs). Basically, the highly active site on SAF NPs nanoagent can trigger in-situ produce toxic •OH in tumor microenvironment (TME) that kill cancer cells for Fenton-reaction-based chemodynamic therapy (CDT). The porous structure of SAF NPs can serve as delivery platforms to package and programmed release chemotherapeutic drug doxorubicin (DOX) to enhance chemotherapy (CT) efficiency. The nanoplatform was simultaneously in-situ mineralized with CaCO 3 and A549 cell membrane (CM) which could avoid DOX leakage during transport in bloodstream and target homologous cancer cells. In addition, overload Ca 2+ decomposed from CaCO 3 triggers mitochondrial dysfunction, induces cytoskeleton collapse and oxidative stress to formulate calcium ions interference therapy (CIT). With the combination of CDT, CT and CIT, the designed multi-synergetic nanoplatform exhibits excellent biocompatibility , specificity and tunable drug release behavior, which has a broad application prospect in tumor therapy.