Functionalized magnetic nanoparticles orchestrate PI3K/AKT signaling to promote apoptosis in breast cancer cells

Abstract

Herein, we report the molecular mechanism by which bare (BMNPs) and citrate-functionalized magnetic nanoparticles (CMNPs) target apoptosis by modulating the PI3K/AKT signaling pathway in breast cancer cells. To achieve this, BMNPs and CMNPs were prepared via co-precipitation and characterized using high-throughput techniques. Furthermore, the as-prepared nanomaterials were evaluated for their anticancer efficacy in modulating apoptosis in breast cancer cells (MCF-7 and MDA-MB-231). The following observations were made: (i) citrate functionalization provided CMNPs with a reactive carboxyl-rich surface, reduced aggregation and improved the zeta potential value (−20.8 mV); (ii) CMNPs demonstrated greater selectivity against MCF-7 and MDA-MB-231 than BMNPs, as revealed by the MTT assay and clonogenic assay; (iii) CMNPs generated high intracellular reactive oxygen species (ROS) and decreased mitochondrial membrane potential in breast cancer cells; (iv) CMNPs demonstrated greater cellular uptake, G1-phase cell-cycle arrest, and anti-migratory activity than BMNPs; and (v) mechanistic validation confirmed that CMNPs suppressed the oncogenic PI3K/AKT signaling pathway and activated the intrinsic mitochondrial apoptotic cascade in breast cancer cells (MCF-7 and MDA-MB-231). These findings reveal the influence of surface chemistry on MNP–biological interactions, offering essential mechanistic insights into nano-oncology and paving the way for the development of innovative nanoplatforms for targeted cancer therapy.