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.