Biomimetic Dual‐Driven Heterojunction Nanomotors for Targeted Catalytic Immunotherapy of Glioblastoma

Abstract

AbstractThe existence of the blood–brain barrier (BBB) and the characteristics of the immunosuppressive microenvironment in glioblastoma (GBM) present significant challenges for targeted GBM therapy. To address this, a biomimetic hybrid cell membrane‐modified dual‐driven heterojunction nanomotor (HM@MnO2‐AuNR‐SiO2) is proposed for targeted GBM treatment. These nanomotors are designed to bypass the BBB and target glioma regions by mimicking the surface characteristics of GBM and macrophage membranes. More importantly, the MnO2‐AuNR‐SiO2 heterojunction structure enables dual‐driven propulsion through near‐infrared‐II (NIR‐II) light and oxygen bubbles, allowing effective treatment at deep tumor sites. Meanwhile, the plasmonic AuNR‐MnO2 heterostructure facilitates the separation of electron–hole pairs and generates reactive oxygen species (ROS), inducing immunogenic tumor cell death under NIR‐II laser irradiation. Furthermore, MnO2 in the tumor microenvironment reacts to release Mn2+ ions, activating the cGAS‐STING pathway and enhancing antitumor immunity. In vitro and in vivo experiments demonstrate that these dual‐driven biomimetic nanomotors achieve active targeting and deep tumor infiltration, promoting M1 macrophage polarization, dendritic cell maturation, and effector T‐cell activation, thereby enhancing GBM catalysis and immunotherapy through ROS production and STING pathway activation.