Enhanced Radiosensitization of Cancer Cell Lines Using Nanoparticles: Mechanisms, Experimental Approaches and Clinical Translation—A Review

Abstract

This review summarizes data from experimental, mechanistic, and translational literature on the radiosensitizing effects of engineered nanoparticles (NPs)—principally gold (AuNPs), silver (AgNPs) and magnetic core–shell hybrid Fe₃O₄@Au constructs—in in vitro cancer models. We summarize common nanoparticle physicochemical characterizations, typical in vitro protocols (cell lines, dosimetry, and endpoints), and major biological readouts (viability, clonogenic survival, γH2AX foci, ROS). Across studies, highZ NPs (Au, Ag) and hybrid formulations frequently increase radiationinduced DNA damage and oxidative stress and reduce clonogenic survival, although the efficacy varies with the particle size, surface chemistry, concentration, cellular uptake, beam energy, and cell type. We synthesize mechanistic evidence supporting three principal mechanisms of nanoparticle radiosensitization—physical dose amplification, chemical ROS amplification, and biological modulation of DNA repair and cell death pathways—and discuss limitations that have delayed clinical translation (toxicity, dosimetry, biodistribution, reproducibility). Finally, we provide a prioritized set of recommendations to accelerate translation to in vivo validation and clinical testing.