M1 macrophage membrane-functionalized nanovesicles for free radical-medicated chemotherapy against liver cancer

Abstract Free radical chemistry including free radical reactive oxygen species (ROS) and reactive nitrogen species (RNS) has received a great deal of attention for cancer treatment due to their ability to produce excessive free radicals, leading to cancer cell death. In this study, we developed M1 macrophage membrane-coated MnO2-silica loaded with doxorubicin (DOX) and a nitric oxide (NO) donor (M1@MS/MnO2/DOX/NO) to enhance therapeutic efficacy for hepatocellular carcinoma therapy. Specifically, superoxide anion O2•− produced from DOX reacted with NO to form ONOO − for RNS-mediated treatment. Meanwhile, Mn2+ produced from the MnO2 layer under a reductive microenvironment functioned as a catalyst to transform endogenous H2O2 into the highly toxic ·OH to achieve ROS-mediated treatment. Our results demonstrated that this novel combination of reactive species therapy synergistically improved the therapeutic efficiency against liver cancer, leading to a significant reduction of cancer cell proliferation, as well as in vivo tumor growth.