biostudies-literatureUnknown19(47)Jung SOptimizing radioenhancer design for cancer therapy has been limited by inconsistent metal comparisons and unclear nanoscale mechanisms. High-Z nanoparticles are expected to enhance radiation effects through increased photoelectric absorption and secondary electron production, with the common assumption that radioenhancement efficacy increases uniformly with atomic number. However, this linear relationship may be oversimplified. Here, we introduce a versatile, supramolecular peptide platform enabling direct and standardized comparison of gadolinium (Gd), bismuth (Bi), and hafnium (Hf) as radioenhancers within a single, biologically targeted framework. This system is based on autoassembled peptide heterodimers (E3-K3) incorporating a flexible chelator (DOTAGA) and variable heavy-chain antiboACS nano40394-40403https://www.ebi.ac.uk/biostudies/studies/S-EPMC12676735biostudies-literatureA Modular Supramolecular Peptide Platform Reveals Atomic-Number-Dependent Mechanisms Driving Radioenhancement.PMC12676735Bou-Gharios JSchmitt JLHarlepp SDetappe ADonzeau MPivot XGasser ANoel GNavarro PLJung SMirjolet CBarbe EfalseA Modular Supramolecular Peptide Platform Reveals Atomic-Number-Dependent Mechanisms Driving Radioenhancement.Optimizing radioenhancer design for cancer therapy has been limited by inconsistent metal comparisons and unclear nanoscale mechanisms. High-Z nanoparticles are expected to enhance radiation effects through increased photoelectric absorption and secondary electron production, with the common assumption that radioenhancement efficacy increases uniformly with atomic number. However, this linear relationship may be oversimplified. Here, we introduce a versatile, supramolecular peptide platform enabling direct and standardized comparison of gadolinium (Gd), bismuth (Bi), and hafnium (Hf) as radioenhancers within a single, biologically targeted framework. This system is based on autoassembled peptide heterodimers (E3-K3) incorporating a flexible chelator (DOTAGA) and variable heavy-chain antibo2025-01-01T00:00:00Z2025 Dec2026-06-05T23:05:27.344Z2026-05-23T03:12:22.152ZS-EPMC126767354125936810.1021/acsnano.5c09326