The Impact of the Reducing Agent on the Cytotoxicity and Selectivity Index of Silver Nanoparticles in Leukemia and Healthy Cells

Silver nanoparticles (AgNPs) are widely studied in oncological nanomedicine, although concerns persist regarding their toxicity, elimination, and tissue accumulation. The biological properties of AgNPs depend on the synthesis method and the reducing agent used, which may influence cytotoxicity and cellular metabolism. This study aimed to evaluate the effect of the reducing agent on the cytotoxicity of AgNPs in leukemia (JURKAT) cell lines and peripheral blood mononuclear cells (PBMCs). AgNPs were synthesized via chemical reduction using glucose (GLU) or polyvinylpyrrolidone (PVP) as reducing agents. Nanoparticles were characterized by UV-Vis, FTIR, DLS, zeta potential, and TEM. Cell viability was assessed using trypan blue exclusion, and cytotoxicity was determined using the MTT assay. UV-Vis analysis showed distinct surface plasmon resonance profiles, and FTIR confirmed characteristic functional groups on the nanoparticle surface. DLS and zeta potential values indicated colloidal stability, with PVP-AgNPs presenting a more negative surface charge. TEM revealed greater size heterogeneity in GLU-AgNPs. GLU-AgNPs induced lower cytotoxicity and higher cell viability in JURKAT and PBMCs compared to PVP-AgNPs (<i>p</i> < 0.05). Leukemia cells were more susceptible to both nanoparticle types than PBMCs, showing a favorable selectivity index for GLU-AgNPs (SI = 2.44). These findings suggest that biocompatible reducing agents may improve the safety profile of AgNPs.