Integrating spatial analysis in the study of silver nanoparticles for radiotherapy: from molecular mechanisms to bio distribution in biological systems

Abstract Silver nanoparticles (AgNPs) have emerged as multifunctional agents in modern oncology due to their tunable physicochemical properties, potent radiosensitizing capacity, and ability to modulate key molecular pathways involved in cancer progression. This review provides an integrated analysis of AgNPs from both molecular and spatial perspectives, emphasizing how size, shape, surface chemistry, and coating influence therapeutic efficacy and biological distribution. We summarize the mechanisms through which AgNPs enhance radiation and drug-induced cytotoxicity – particularly via reactive oxygen species generation, mitochondrial dysfunction, and DNA damage – and highlight their synergistic roles in multimodal treatments such as radiotherapy, chemotherapy, and phototherapy. Special attention is given to spatial biodistribution mapping, using advanced imaging and analytical methods (PET, SPECT, MRI, ICP-MS, and hyperspectral imaging) to quantify nanoparticle localization and clearance in vivo . Current preclinical findings are critically evaluated alongside safety and regulatory considerations, underscoring the need for standardized synthesis protocols, long-term toxicity studies, and imaging-guided design strategies. Collectively, these insights provide a framework for translating AgNP-based nanomedicine from experimental studies to clinically applicable, patient-specific cancer therapies.