Wireless chargeable gold Yarnball-mediated mitochondrial depolarization for dendritic cell detainment in programmed brain tumor immunotherapy

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.