Cationic\nMagnetic Nanoparticles Activate Natural Killer\nCells for the Treatment of Glioblastoma

The\nblood–brain barrier (BBB) and the immunosuppressive\nmicroenvironment of glioblastoma (GBM) severely hinder the infiltration\nand activity of natural killer (NK) cells, thereby reducing their\nclinical efficacy in GBM treatment. To address this challenge, we\nintroduced an engineered living material, HEFDS-NK cells, designed\nto enhance the penetration of NK cells across the BBB and improve\ntheir cytotoxicity against GBM. HEFDS comprises magnetic nanoparticles\nmodified using cationic polyethylenimine (PEI), selenocysteine (Sec),\nand sodium hyaluronate (HA) and cocultured with NK cells to form HEFDS-NK\ncells. With the assistance of HA and magnet targeting, HEFDS-NK cells\ncan effectively cross the BBB and localize at the GBM site. Moreover,\nPEI enhances the expression of C–X–C chemokine receptor\ntype 4 (CXCR4) and C–C chemokine receptor type 4 (CCR4) on\nNK cells, thereby improving their recognition and cytotoxicity against\nGBM. Additionally, Sec boosts the immune activity of NK cells against\nGBM. Upon recognizing GBM, the activated HEFDS-NK cells produce Granzyme\nB, Perforin, and IFN-γ, ultimately achieving effective therapy\nfor GBM. This study demonstrates an effective treatment of GBM while\nenhancing NK cell activity and their ability to penetrate the BBB,\nproviding an innovative and high-precision therapeutic approach for\nGBM.