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As a kind of reactive oxygen species (ROS)-mediated cancer therapy modality, chemodynamic therapy (CDT) has been extensively explored. However, the insufficient endogenous H2O2 and the intracellular redox homeostasis greatly obstruct the anticancer efficacy. Developing multifunctional nanomedicine which can address these issues is appealing. Herein, 4T1 cancer cell membrane (CM)-coated glutathione (GSH)-responsive biodegradable biomimetic nanoreactor, CaO2@MnO2–DOX@CM, was fabricated for tumor oxidative stress amplification enhanced self-supplying H2O2 chemodynamic therapy and synergistic chemotherapy. Highly expressed GSH in the tumor cells could trigger the biodegradation of CaO2@MnO2–DOX@CM, and the Fenton-like catalyst Mn2+ and chemotherapy drug doxorubicin (DOX) were released. The unprotected CaO2 further reacted with water to generate a large amount of H2O2 and Ca2+. The self-supplying H2O2 not only reacted with Mn2+ to generate hydroxyl radical (•OH) but also sped up the biodegradation of the nanoreactor. Furthermore, the MnO2-mediated GSH depletion and the Ca2+-overloading-induced mitochondria dysfunction could further enhance the CDT efficiency. Thus, the glutathione-responsive biodegradable core–shell nanoparticles achieved MRI-guided synergistic chemo–chemodynamic therapy, showing bright prospect for highly efficient tumor treatment. [ABSTRACT FROM AUTHOR]

Glioma, the most common primary brain tumor, is highly invasive and grows rapidly. As such, the survival of glioma patients is relatively short, highlighting the vital importance of timely diagnosis and treatment of glioma. However, the blood brain barrier (BBB) and the non-targeting delivery systems of contrast agents and drugs greatly hinder the effective glioma imaging and therapy. Fortunately, in recent years, investigators have constructed various biomimetic delivery platforms utilizing the exceptional advantages of biomimetic nanocomposites, such as immune evasion, homologous targeting ability, and BBB penetrating ability, to achieve efficient and precise delivery of substances to glioma sites for improved diagnosis and treatment. In this concept, we present the application of these biomimetic nanocomposites in fluorescence imaging (FI), magnetic resonance imaging (MRI), and multi-modal imaging, as well as in chemotherapy, phototherapy, and combined therapy for glioma. Lastly, we provide our perspective on this research field., (© 2024 Wiley-VCH GmbH.)

Hydroxyl radical (·OH), as the most deleterious reactive oxygen species, is believed to be the etiological agent for many diseases and aging. An altered ·OH level has been confirmed in certain types of superoxide dismutase (SOD) mutation, but the regulation of ·OH by SOD in situ is still controversial or unclear because of the lack of effective tools to detect ·OH in the biological environment. Herein we report the first two-photon excitable molecular probe (P2) for ·OH, which is able to track the subtle fluctuation of ·OH level both in vitro and in vivo with high sensitivity and specificity. The probe was successfully applied to visualize ·OH variations in a variety of SOD1-involved biological processes, confirming that the inhibited enzymatic activity and down-regulated expression of SOD1 both lead to elevated intracellular ·OH level. This is the first report to visually reveal the relationship between SOD1 and ·OH level with a molecular tool.