ABSTRACT
Superparamagnetic iron oxide nanoparticles (SPIONs) have garnered significant attention in the medical sector due to their exceptional superparamagnetic properties and reliable tracking capabilities. In this study, we investigated the immunotoxicity of SPIONs with a modified surface to enhance hydrophilicity and prevent aggregate formation. The synthesized SPIONs exhibited a remarkably small size (~4 nm) and underwent surface modification using a novel "haircut" reaction strategy. Experiments were conducted in vitro using a human monocytic cell line (THP-1). SPIONs induced dose-dependent toxicity to THP-1 cells, potentially by generating ROS and initiating the apoptotic pathway in the cells. Concentrations up to 10 µg/mL did not affect the expression of Nrf2, HO-1, NF-κB, or TLR-4 proteins. The results of the present study demonstrated that highly hydrophilic SPIONs were highly toxic to immune cells; however, they did not activate pathways of inflammation and immune response. Further investigation into the mechanisms of cytotoxicity is warranted to develop a synthetic approach for producing effective, highly hydrophilic SPIONs with little to no side effects.
ABSTRACT
Serial analysis of circulating tumor DNA (ctDNA) over the disease course is emerging as a prognostic, predictive and patient-monitoring biomarker. In the metastatic setting, several multigene ctDNA assays have been approved or recommended by regulatory organizations for personalized targeted therapy, especially for lung cancer. By contrast, in nonmetastatic disease, detection of ctDNA resulting from minimal residual disease (MRD) following multimodal treatment with curative intent presents major technical challenges. Several studies using tumor genotyping-informed serial ctDNA profiling have provided promising findings on the sensitivity and specificity of ctDNA in predicting the risk of recurrence. We discuss progress, limitations and future perspectives relating to the use of ctDNA as a biomarker to guide targeted therapy in metastatic disease, as well as the use of ctDNA MRD detection to guide adjuvant treatment in the nonmetastatic setting.
