Cationic Magnetic Nanoparticles Activate Natural Killer Cells for the Treatment of Glioblastoma

Abstract

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