A multifunctional nanoplatform combining self-supplied H2O2 production with CO delivery for multimodal anti-tumor therapy

Abstract

Disrupting the reactive oxygen species (ROS) homeostasis in cancer cells offered a therapeutic modality for anti-tumor treatment. However, the therapeutic efficacy of conventional chemodynamic therapy (CDT) was impaired by the insufficient H₂O₂ concentration in the tumor microenvironment (TME). Herein, we report the preparation of a multifunctional nanoplatform CaO₂@PDA–Cu@MnCO with self-supplied H₂O₂ production and carbon monoxide (CO) delivery in the TME for efficient multimodal therapy. The nanoplatform consists of a calcium peroxide (CaO₂) carrier, with which the surface was covered by Cu²⁺-doped polydopamine layers, and a covalently loaded manganese carbonyl (MnCO) donor. The nanoplatform specifically responded to the acidic TME, thereby releasing Ca²⁺ and H₂O₂ that was further decomposed into hydroxyl radicals (˙OH) via the Cu ion catalyzed Fenton-like reaction. Meanwhile, the released CO under 808 nm light irradiation led to mitochondrial dysfunction and increased the accumulation of intracellular ROS. Furthermore, the Ca²⁺ overloading could result in calcification of the cancer cells. Consequently, CaO₂@PDA–Cu@MnCO showed impressive eradication efficacy for 4T1 cancer cells with a low IC₅₀ value, thus offering a promising therapeutic modality for cancer treatment.