Microwave-Responsive Nanoplatform with Robust ROS Generation and Inhibiting Effects of Two-Component System and Quorum Sensing for the Treatment of MRSA-Induced Osteomyelitis

The hypoxic environment of deep tissue and the weak energy of microwave (MW) are still the major limitations of MW catalytic therapy. In this work, an MW-responsive nano-platform consisting of an Mn-doped porphyrin metal–organic framework loaded with calcium peroxide (Mn_0.1PCC) is designed to regulate the microenvironment of the injection site and enhance the generation of reactive oxygen species. The excellent MW absorbing properties of Mn_0.1PCC improve the Fenton reaction between hydrogen peroxide formed by the hydrolysis of calcium peroxide and released Mn²⁺ generating more hydroxyl radicals under MW. This process does not consume the oxygen substrate and even produces oxygen to improve the hypoxic environment. Therefore, at a low and safe concentration (125 µg mL⁻¹), the antibacterial rate of Mn_0.1PCC against 4 × 10⁸ CFU mL⁻¹ of methicillin-resistant Staphylococcus aureus (MRSA) after MW irradiation for 15 min is 99.71% ± 0.18%. Mn_0.1PCC, upon exposure to MW, prevents the recurrence of bacterial infections and overcomes drug resistance by inhibiting quorum sensing and the two-component system of MRSA. It can also induce macrophage M1 polarization, up-regulate the pro-inflammatory factor tumor necrosis factor-α, and enhance the phagocytosis of macrophage to bacteria. This strategy provides insights into the development of high-performance MW-responsive nanocomposites for the treatment of infections in deep tissues. © 2024 The Author(s). Advanced Functional Materials published by Wiley-VCH GmbH.