Gold nanostructure-based cancer photothermal therapy: a comprehensive systematic review, meta-analysis, and dose–response evaluation

This globally first systematic review and meta-analysis quantitatively evaluates the efficacy, safety, and dose–response relationships of gold (Au) nanoparticle-mediated photothermal therapy (PTT). A systematic search was conducted across four major databases for preclinical studies published between 2015 and 2025, adhering to PRISMA guidelines (PROSPERO registration: CRD420251250129). Random-effects meta-analysis was employed to pool effect sizes for tumor growth inhibition and temperature elevation. Furthermore, a dose–response meta-regression and subgroup analysis were performed to elucidate the relationship between nanoparticle concentration, radiation intensity and therapeutic efficacy. The OHAT and SYRCLE tools were used to rate the quality of the included studies. Ultimately, 162 (113 in-vitro and 72 in-vivo) and 64 studies satisfied the inclusion criteria for the systematic review and quantitative meta-analysis, respectively. The best photothermal conditions were a wavelength of 808 nm, a laser intensity of 0.5–3.0 W/cm 2 , and an irradiation time of 5–10 min. Also, among nanostructure morphologies, Au nanorods (optimal size ~80 nm) demonstrated superior photothermal efficiency. The pooled analysis of the two primary variables revealed a strong therapeutic response, characterized by a mean intra-tumoral temperature elevation of 15.30 °C (95% CI 13.06 °C to 17.54 °C; p < 0.001), and a significant tumor volume reduction of − 832.21 mm 3 (95% CI − 1016.08, − 648.34 mm 3 ; p < 0.001) relative to controls. Dose–response meta-regression identified a nonlinear efficacy pattern, with a therapeutic plateau observed at concentrations between 50 and 100 μg/mL, suggesting minimal gains beyond this range. Additionally, triple-combination strategies achieved the highest synergy index (2.45), and safety evaluations confirmed favorable biocompatibility at doses ≤15 mg/kg. As the first comprehensive global analysis, this study quantitatively validates Au nanoparticle PTT as an effective preclinical modality, defined by a distinct dose–response profile, predictable biological outcomes, and substantial synergistic potential.