Research on the Effect of NK Cells Based on Functionalized Magnetic Beads on Cervical Cancer Mice.

Abstract

In recent years, the incidence of tumors has shown an increasing trend, while traditional treatment methods such as surgery, radiotherapy, and chemotherapy exhibit certain limitations. Immunotherapy has been extensively investigated in the field of cancer treatment due to its advantages of high specificity in recognition, significant inhibition of tumor growth and proliferation, and the absence of adverse effects on the structure and function of normal tissue cells. Natural killer (NK) cells, as crucial components of the innate immune system, play a pivotal role in antitumor immune responses. In this study, a magnetic nanocarrier loaded with NK cells was constructed to combine magnetic targeting with NK immunotherapy. By integrating magnetic targeting with NK cell immunotherapy, this system enhances NK cell infiltration at tumor sites through external magnetic field guidance, thereby improving the tumor-killing efficacy. The main research contents are as follows: nanoscale Fe₃O₄@Agarose beads (AMbs) were fabricated and carboxylated to obtain carboxylated Fe₃O₄@Agarose-COOH beads with a particle size of approximately 200 nm. Using these carboxylated beads as carriers, the "AMbs-MCD16-NK" magnetic targeting system was constructed by conjugating the aptamer MCD16, which corresponds to the CD16 surface protein on NK cells. A U14 mouse cervical cancer tumor-bearing model was established to evaluate the in vivo antitumor efficacy and biosafety of the system. The results demonstrated that the "AMbs-MCD16-NK" system exhibited excellent tumor-targeting capability at the tumor site under magnetic field regulation, achieving a tumor inhibition rate of 57.32 ± 12.98% in mice. This system effectively inhibited tumor cell proliferation, induced apoptosis and necrotic lesions in tumor tissues, promoted NK cell infiltration into the tumor site, and regulated the release of proinflammatory cytokines (e.g., interferon-γ (IFN-γ) and granzyme B (GZMB)), thereby enhancing NK cell cytotoxicity against tumor cells. Detection of a series of biological indicators in mice confirmed that the "AMbs-MCD16-NK" system possessed favorable biosafety. Collectively, the "AMbs-MCD16-NK" system developed in this study enhances NK cell-based immunotherapy through magnetic targeting, providing a strategy for NK cell-mediated cancer treatment.