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

in ACS nano by Zhi-Yong Rao, Jing Kuang, Ting Pan, You-Teng Qin, Qian-Xiao Huang, Yu-Liang Sun, Kai Zhao, Xiao-Kang Jin, Chi-Hui Yang, Shi-Man Zhang, Yu Yan, Xian-Zheng Zhang

TLDR

  • A novel engineered living material, HEFDS-NK cells, has been designed to enhance the penetration of NK cells across the blood-brain barrier and improve their cytotoxicity against glioblastoma (GBM).
  • The HEFDS-NK cells effectively cross the blood-brain barrier and localize at the GBM site, producing Granzyme B, Perforin, and IFN-γ to achieve effective therapy for GBM.

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.

Overview

  • The study aimed to design an engineered living material, HEFDS-NK cells, to enhance the penetration of natural killer cells across the blood-brain barrier and improve their cytotoxicity against glioblastoma (GBM).
  • The HEFDS material consists of magnetic nanoparticles modified with cationic polyethylenimine (PEI), selenocysteine (Sec), and sodium hyaluronate (HA) and cocultured with NK cells to form HEFDS-NK cells.
  • The study aimed to achieve effective therapy for GBM by overcoming the limitations of NK cells' ability to infiltrate the brain and recognize GBM cells.

Comparative Analysis & Findings

  • The HEFDS-NK cells were found to effectively cross the blood-brain barrier and localize at the GBM site with the assistance of HA and magnet targeting.
  • PEI in HEFDS-NK cells enhanced the expression of C-X-C chemokine receptor type 4 (CXCR4) and C-C chemokine receptor type 4 (CCR4) on NK cells, improving their recognition and cytotoxicity against GBM.
  • The study demonstrated that activated HEFDS-NK cells produced Granzyme B, Perforin, and IFN-γ, achieving effective therapy for GBM.

Implications and Future Directions

  • The study provides an innovative and high-precision therapeutic approach for GBM treatment, potentially increasing the efficacy of NK cell-based therapies.
  • Future studies could explore the optimal dosage and duration of HEFDS-NK cells treatment and the combination with other therapeutic modalities.
  • The study highlights the potential of engineered living materials to overcome the challenges of delivering immunotherapies to the brain.
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