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Ischemic stroke is a leading cause of death and disability worldwide, and the main goals of stroke treatment are to destroy the thrombus to recanalize blood vessels and protect tissue from ischemia/reperfusion injury. However, current recanalization therapies have serious limitations and there are few neuroprotection methods. Hence, an artificial nanoplatform loaded with anti‐Repulsive Guidance Molecule a monoclonal antibody (anti‐RGMa) and coated with microglia membrane (MiCM) is reported for stroke treatment, namely MiCM@PLGA/anti‐RGMa/Fe3O4@PFH (MiCM‐NPs). Tail vein injection of MiCM‐NPs targeted the ischemia‐damaged endothelial cells because of the MiCM, then superparamagnetic iron oxide (Fe3O4) and anti‐RGMa are released after external low‐intensity focused ultrasound (LIFU) exposure. The thrombus is destroyed by LIFU‐induced "liquid‐to‐gas" phase transition and cavitation of perfluorohexane (PFH) as well as Fe3O4 movements induced by an external magnetic field. Anti‐RGMa protected the ischemic region from ischemia/reperfusion injury. The nanoplatform enabled visualization of the thrombus by ultrasound/photoacoustic imaging when the clot is in an extracranial artery. Importantly, in vivo animal studies revealed good safety for MiCM‐NPs treatment. In conclusion, this nanoplatform shows promise as an ischemic stroke treatment strategy combining targeted delivery, recanalization, and neuroprotection. [ABSTRACT FROM AUTHOR]

Background: Chemodynamic therapy (CDT) is recognized as a promising cancer treatment. Recently, copper sulfide nanostructures have been extensively employed as Fenton-like reagents that catalyze the formation of acutely toxic hydroxyl radicals (·OH) from hydrogen peroxide (H 2 O 2 ). However, CDT therapeutic potency is restricted by the tumor microenvironment (TME), such as insufficient amounts of hydrogen peroxide, excessive glutathione levels, etc. To address these disadvantages, glucose oxidase (GOx) or catalase (CAT) can be utilized to enhance CDT, while low therapeutic efficacy still inhibits their future applications. Our previous study revealed that mild photothermal effect could boost the CDT catalytic effectiveness as well as GOx enzyme activity over a range. Results: We engineered and constructed a hollow CuS nanoplatform loaded with GOx and CAT, coating with macrophage membranes (M@GOx-CAT@CuS NPs). The nanoplatforms allowed enhancement of the reactive oxygen species creation rate and GOx catalytic activeness of CDT through mild phototherapy directed by photoacoustic imaging. After actively targeting vascular cell adhesion molecule-1 (VCAM-1) in cancer cells mediated by macrophage membrane coating, M@GOx-CAT@CuS NPs released GOx and CAT under near-infrared irradiation. GOx catalyzed the formation of H 2 O 2 and gluconic acid with glucose, creating a better catalytic environment for CDT. Meanwhile, CAT-catalyzed H 2 O 2 decomposition to generate sufficient oxygen, appropriately alleviating the oxygen shortage in the TME. In addition, starvation effects decreased adenosine triphosphate levels and further underregulated heat shock protein expression to reduce the heat resistance of tumor cells, resulting in a better mild phototherapy outcome. Both in vitro and in vivo experiments demonstrated that the newly developed M@GOx-CAT@CuS nanoplatform has remarkable synergistic anticancer therapeutic effects. Conclusion: The cascade reaction-enhanced biomimetic nanoplatform opens up a new avenue for precision tumor diagnostic and therapeutic research., Competing Interests: Competing interests: The authors declare no financial competing interests., (Copyright © 2024 Ziqun Chen et al.)