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. 2025 Sep 19.
doi: 10.1227/neu.0000000000003731. Online ahead of print.

The Potential of Magnetic Targeted Natural Killer Cell Therapy for Glioblastoma: An in Vivo Study of Natural Killer Cells Loaded With Low-Temperature Synthesized Folic Acid-Modified Superparamagnetic Iron Oxide Nanoparticles

Pao-Chun Lin  1   2 , Ya-Jyun Liang  1 , Wei-Ting Kuo  1 , Feng-Huei Lin  1   3 , Fon-Yih Tsuang  4   5
Affiliations

The Potential of Magnetic Targeted Natural Killer Cell Therapy for Glioblastoma: An in Vivo Study of Natural Killer Cells Loaded With Low-Temperature Synthesized Folic Acid-Modified Superparamagnetic Iron Oxide Nanoparticles

Pao-Chun Lin et al. Neurosurgery. .

Abstract

Background and objectives: Glioblastoma (GBM) is a highly malignant brain tumor with limited treatment options. While natural killer (NK) cell-based immunotherapy shows promise in cancer treatment, effective tumor targeting remains a challenge. This study investigates the use of folic acid-modified superparamagnetic iron oxide nanoparticles (SPIONs-PEG-FA) to magnetize NK cells, enabling them to accumulate at the tumor site under an external magnetic field while retaining their cytotoxic activity against GBM cells.

Methods: SPIONs-PEG-FA were synthesized using PEGylation and coprecipitation to ensure efficient NK cell uptake. Their successful synthesis was confirmed through material characterization, including X-ray diffraction, Fourier transform infrared spectroscopy, transmission electron microscopy, and dynamic light scattering. In vitro studies evaluated their safety, cellular uptake, and cytolytic activity, whereas in vivo experiments assessed tumor targeting and therapeutic efficacy in GBM-bearing mice.

Results: SPIONs-PEG-FA-loaded NK cells were successfully developed for targeted GBM therapy. In vitro studies confirmed their safety and effectiveness against GBM tumor cells, whereas transmission electron microscopy analysis verified the cellular uptake of SPIONs-PEG-FA by NK cells. In vivo experiments in GBM-bearing mice demonstrated improved tumor targeting, enhanced cytolytic efficiency, and overall safety of SPIONs-PEG-FA-loaded NK cells.

Conclusion: SPIONs-PEG-FA-loaded NK cells represent a promising approach for targeted GBM therapy. Their successful synthesis and characterization, coupled with in vitro and in vivo validation, highlight their potential for improved therapeutic outcomes. This magnetic field-guided NK cell therapy offers a promising strategy for overcoming challenges in GBM treatment.

Keywords: Glioblastoma; Immunotherapy; NK cell; Superparamagnetic iron oxide.

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