Silver nanoparticles as breast cancer chemosensitizers: A systematic scoping review of speciation, combination efficacy, formulation, and safety.

PURPOSE: This systematic scoping review critically assessed whether silver nanoparticles (AgNPs) can sensitize breast cancer to cytotoxic drugs and distinguished between experimentally supported mechanisms and hypothesis-level claims of subtype-specific responses. METHODS: Searches were conducted in PubMed/MEDLINE, Scopus, and Web of Science Core Collection from January 2010 to January 2026 and complemented by backward citation searching and searches by DOI with the same eligibility criteria. Selected studies were quantitatively extracted and appraised using an adapted version of the Toxicological Data Reliability Assessment Tool (ToxRTool). RESULTS: The evidence base is largely composed of in vitro studies, and there are few studies on breast cancer in animals and no clinical trials on this topic. Combination studies have assessed doxorubicin, cisplatin, paclitaxel, capecitabine, and 5-fluorouracil; however, studies that simultaneously measure drug response and dosimetry of Ag(I) in cells are rare. CONCLUSION: Despite preclinical chemosensitizing activity, preclinical findings for AgNPs have been somewhat inconsistent, and therapeutic windows for specific subtypes have yet to be defined owing to the lack of consistency with silver speciation and drug response. Standardized dose metrics, orthogonal Ag(0)/Ag(I) speciation, formal combination analysis, subtype-matched models, and tumor-to-liver and tumor-to-spleen dosimetry should be used for studies to enable translation, and baseline silver and selenium statuses should be evaluated as exploratory covariates.