摘要
Activation of the innate immune cascade offers a potential strategy to inhibit glioblastoma (GBM) proliferation. However, immune privilege along with blood-brain barrier (BBB) and low immunogenicity of GBM often limits lymphocyte infiltration. In this study, a wireless charging mitochondria-targeted nanoantenna (WINA) served as a membrane-disrupting and mitochondria-depolarizing agent was developed for interning dendritic cells and a programmed immunotherapy. By convection-enhanced delivery, membrane-disrupting cationic triphenylphosphine (TPP)-conjugated polyglutathione (pGSH) on WINA improves tumor penetration to deep area and targets mitochondria. Under high-frequency magnetic field (HFMF) irradiation, WINA generates reactive oxygen species (ROS) from hydrogen peroxide (H2O2) in mitochondria and drives mitochondrial depolarization through eddy current generation. The depolarization further causes the dissipation of mitochondrial membrane potential (MMP), leading to the release of damage-associated molecular patterns (DAMPs). This process activates dendritic cells, thereby enhancing the effective infiltration of T cells to the brain tumor. Furthermore, transcriptome analysis of brain tumors revealed that key genes such as Cd8a, Ifng, Tnf, and Il1b, which are critical for T cell activation. In whole-brain diffusion MRI, fiber tracing of the M1-TH and S1HL-Cpu tracts was explored after treatment, indicating improved brain function. Combined with immune checkpoint therapy, this approach resulted in antitumor activity and tumor growth inhibition.
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•A wireless charging mitochondria-targeted nanoantenna (WINA) served as a mitochondria-depolarizing agent was developed for interning dendritic cells and immunotherapy.•Under high-frequency magnetic field (HFMF) irradiation, WINA generates reactive oxygen species (ROS) from hydrogen peroxide (H2O2) in mitochondria and drives mitochondrial depolarization.•The transcriptome analysis of brain tumors revealed that key genes such as Cd8a, Ifng, Tnf, and Il1b, which are critical for T cell activation.