Glioblastoma Targeting Immunotherapy with Magnetic Nanoparticle-Loaded Natural Killer Cells

Introduction: Glioblastoma (GBM) is an aggressive brain cancer where increased NK cell infiltration leads to better treatment outcomes. NK cells hold promise in cancer therapy as they can target and destroy tumor cells without prior sensitization. However, NK cells don't target tumors via antigens but rely on external cues for guidance. Hence, our goal was to develop an immune cell delivery system for GBM using surface modified superparamagnetic nanoparticles loaded NK cells, allowing their accumulation at the tumor site through an external magnetic field.

Methods: GBM is a highly malignant glioma, and greater NK cell infiltration correlates with improved treatment results. NK cells offer potential for cancer therapy without the need for antigen recognition. They rely on external cues and gradients for homing to disease sites. Our study aimed to create an immune cell delivery system by labeling NK cells with surface modified superparamagnetic nanoparticles to enhance their accumulation at GBM tumor sites using an external magnetic field.

Results: In this research, we successfully synthesized superparamagnetic nanoparticles, as confirmed by FTIR, XRD, and EDS elemental analysis. We also achieved surface modification to enhance NK cell endocytosis and surface attachment. These nanoparticles were approximately 300 nm in size, ideal for cellular endocytosis, and demonstrated superparamagnetism, confirmed by SQUID analysis. In migration tests with NK-92 cells, surface modified superparamagnetic nanoparticles showed the ability to be guided by an external magnetic field, indicating its potential for targeted guidance. Furthermore, the study observed a 50% increase in glioma cell lysis compared to the control group, confirming tumor cytolytic activity.

Conclusion : Surface modified superparamagnetic nanoparticles have been successfully synthesized and characterized, with a small size (314.7±6.2 nm), a negative Zeta potential (-29.14±0.94 mV), and low cytotoxicity. In migration tests, these nanoparticles effectively guided NK cells towards an external magnetic field, enhancing their cytolytic activity. This suggests their potential value in immunotherapy to boost immune cell function. Further validation in animal models will confirm their efficacy in migration and tumor cell elimination.