Quantification and biological evaluation of ZnxFe3−xO4 nanoparticle stiffness in a drug delivery system of MCF-7 cancer cells

Abstract

The delivery of nanoparticles (NPs) to tumors remains challenging despite significant advancements in drug delivery technologies. Addressing this issue requires the establishment of quantitative and reliable criteria to evaluate the cellular absorption of NPs. The mechanical characteristics of NPs and their interaction with cells play a crucial role in cellular drug delivery by influencing cellular internalization. In particular, NPs' stiffness has emerged as a key factor affecting cellular uptake and viability. In this study, we synthesized Zn_xFe_3−xO₄ NPs with varying Zn doping concentrations and conducted an extensive measurement process to investigate the impact of NP stiffness on cellular uptake and the viability of cancerous cells. Initially, the stiffness of the NPs was measured using two methods: single-molecule force spectrometry of atomic force microscopy (SMFS-AFM) and cation distribution as chemical structure analysis. The influence of NP stiffness on intracellular behavior was examined by assessing cellular uptake and viability at different time points during the incubation period. The results obtained from both stiffness measurement methods exhibited consistent trends. NPs with higher stiffness exhibited enhanced cellular uptake but exhibited reduced cellular viability compared to the lower-stiffness NPs. Our findings provide valuable insights into the influence of Zn doping concentration on the mechanical properties of Zn_xFe_3−xO₄ NPs and their consequential impacts on cellular internalization. This study contributes to an improved comprehension of the mechanisms underlying cellular uptake and facilitates advancements in the field of drug transport, thereby enhancing the efficiency of NP-based drug delivery.