Abstract: Breast cancer (BC) is the most frequently diagnosed cancer in women worldwide. Chemodynamic therapy (CDT), photothermal therapy (PTT), and ion interference therapy (IIT), used in combination, represent a common treatment. In this study, the platelet membrane-camouflaged copper doped CaO2 biomimetic nanomedicines have been developed for breast cancer treatments. Copper doped CaO2 nanoparticles firstly coated by polydopamine (PDA), and subsequently camouflaged by platelet membrane (PM) to form platelet membrane-camouflaged copper doped CaO2 biomimetic nanomedicines (Cu-CaO2@PDA/PM). The as-fabricated Cu-CaO2@PDA/PM multifunctional nanomedicines could decompose within the tumor microenvironment to release Ca2+ for ion interference therapy, and the generated H2O2 could perform a Fenton-like reaction with assistance of loaded copper ions to produce ·OH, thus realizing chemodynamic therapy. In addition, the copper ions could also consume glutathione and weaken its ability to scavenge reactive oxygen species, which was conducive to amplifying the effect of oxidative stress. The coating of polydopamine layer could achieve local hyperthermia of tumor site, and the surface modification of platelet membrane could enhance the targeting and biocompatibility of nanomedicines. In vivo and in vitro tests demonstrated that the developed Cu-CaO2@PDA/PM biomimetic nanomedicines offer a promising biomimetic nanoplatform for efficient multimodal combination therapy for breast cancer.

Keywords: biomimetic nanomedicines, synergistic therapy, chemodynamic therapy, photothermal therapy, ion interference therapy