Green-Synthesized Silver Nanoparticles as Cytotoxic Agents in Triple-Negative Breast Cancer: A Review of ROS-Mediated Apoptosis Mechanisms

Abstract

Triple-negative breast cancer (TNBC) represents one of the most aggressive and therapeutically challenging subtypes of breast cancer due to the absence of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression. The limited targeted therapy options and high recurrence rates have driven the search for novel anticancer agents. Green-synthesized silver nanoparticles (AgNPs) derived from plant extracts have emerged as promising cytotoxic agents owing to their unique physicochemical properties, environmental compatibility, and enhanced biocompatibility. This systematic review aims to analyze the cytotoxic potential of plant-mediated green-synthesized AgNPs against TNBC cells and to elucidate the reactive oxygen species (ROS)-mediated apoptosis mechanisms based on current research findings. Literature searches were conducted across Google Scholar, PubMed, and ScienceDirect databases using relevant keywords, and selected articles were analyzed descriptively. The results demonstrate that green-synthesized AgNPs, characterized by sizes ranging from 10 to 100 nm, spherical morphology, and negative zeta potential, exhibit significant cytotoxic activity against TNBC cell lines, particularly MDA-MB-231, through dose-dependent and time-dependent mechanisms. The primary mechanism of action involves intracellular ROS overproduction that induces oxidative stress, mitochondrial dysfunction, upregulation of pro-apoptotic proteins such as Bax and p53, downregulation of anti-apoptotic Bcl-2, activation of caspase cascades, and DNA damage, ultimately leading to programmed cell death via the intrinsic apoptotic pathway. Plant-derived phytochemical capping agents further contribute synergistically to these effects. These findings establish a strong scientific foundation for the development of plant-based nano-chemotherapeutic agents as selective, safer, and more effective alternatives for TNBC treatment.