Dose enhancement by gold, iron oxide, bismuth oxide, and platinum nanoparticles in radiotherapy: a comprehensive meta-analysis

Abstract

This first global comprehensive meta-analysis of 64 studies compares four metal (gold (Au), iron oxide (IO), bismuth oxide (BO), platinum (Pt)) nanoparticles (NPs) as cancer radiosensitizers. Following PRISMA guidelines, we searched PubMed/Medline, Scopus, Web of Science, and Cochrane Library through November 2025 for studies on four metal NPS as cancer radiosensitizers. Meta-analysis calculated pooled dose enhancement factor (DEF) with comprehensive publication bias assessment (Egger's, Begg's, Trim-and-Fill, Fail-Safe N) and sensitivity analyses. Subgroup analyses examined nanoparticle size (<= 10 nm, 10-30 nm, > 30 nm), radiation energy (<= 100 keV, 100-250 keV, > 250 keV), and cancer cell line effects. Meta-regression evaluated size as a continuous predictor. Analysis of 95 independent data comparing four NPs revealed BO as most efficacious (0.575; 95 CI: 0.352-0.798; p = 0.001), followed by Au (0.395; 95 CI: 0.317-0.474; p = 0.001) and IO (0.293; 95 CI: 0.153-0.433; p = 0.001). Pt showed highest point estimate (0.780; 95 CI: 0.306-1.255; p = 0.001) but critically fragile evidence (Fail-Safe N = 2). Smaller NPs (<= 10 nm, 0.500; 95 CI: 0.300-0.700) demonstrated 60 greater efficacy than 10-30 nm particles (0.312; 95 CI: 0.180-0.430). Orthovoltage radiation (<= 100 keV0.710; 95 CI: 0.410-1.150) produced 2-fold greater enhancement than megavoltage (> 250 keV, 0.350; 95 CI: 0.240-0.460). Sensitivity analysis confirmed no influential outliers, with bismuth showing exceptional robustness (+/- 6 variation). BO is the optimal radiosensitizer, demonstrating highest efficacy with unbiased evidence. Smaller NPs (<= 10 nm) and orthovoltage radiotherapy protocols maximize radiosensitization enhancement.