CO-FUNCTIONALIZED SILVER NANOPARTICLES WITH FOLIC ACID AND CHELIDONIC ACID: DIFFERENTIAL CYTOTOXIC AND OXIDATIVE STRESS RESPONSES IN HELA AND L929 CELLS

Abstract

Silver nanoparticles exhibit strong anticancer potential despite causing toxicity and reactive oxygen species (ROS) accumulation in healthy cells. This study aims to develop a nanoparticle system that selectively targets cancer cells while reducing the toxicity and ROS activity of silver nanoparticles in healthy cells. In this context, folic acid (FA) and chelidonic acid (CA) were conjugated to silver nanoparticles. FA enhanced cytotoxicity by increasing targeting via folate receptors overexpressed in cancer cells, while CA provided a protective effect by increasing antioxidant capacity in healthy cells. Thus, a dual-functional nanoparticle conjugate (AgNP/FA/CA) was obtained.The physicochemical characterization of the obtained conjugates was performed using dynamic light scattering (DLS), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FT-IR) analyses. According to DLS results, the hydrodynamic size of the AgNP/FA/CA conjugate was determined to be 178.3 nm, and its zeta potential was −7.5 ± 3.55 mV. Characterization analyses confirmed that the particles were colloidally stable, monodisperse (PDI: 0.1), and spherical in morphology. FT-IR analyses demonstrated that the conjugates were successfully functionalized with FA and CA.According to cell viability (MTT assay) results, the AgNP/FA/CA application maintained viability in the L929 fibroblast cell line, while it caused significant cytotoxicity in HeLa cancer cells. Oxidative Stress Index (OSI) results, calculated using Total Oxidant Status (TOS) and Total Antioxidant Status (TAS) data, showed that the conjugate produced different oxidative stress responses depending on the cell type. In L929 cells, the antioxidant effect of CA caused the OSI value to fall below that of the control group (118.07) to 92.32, indicating that cellular stress was suppressed. In contrast, in HeLa cells, the AgNP/FA/CA conjugate induced high levels of oxidative stress (OSI: 216.20) by exceeding the adaptive antioxidant capacity and exhibited antitumor effects.In conclusion, the AgNP/FA/CA conjugate offers a dual-functional and potentially safe nanotherapeutic approach that selectively targets cancer cells while suppressing systemic toxicity in healthy tissues.