Design mechanisms and biomedical applications of peptide-metal chelates in antimicrobial therapy, tumor theranostics, and integrated diagnosis-treatment systems

The growing global antimicrobial resistance crisis and limitations of conventional cancer therapies call for innovative biomedical strategies. Peptide-metal chelates are promising multifunctional biomaterials that leverage peptide-metal ion synergy to overcome traditional therapeutic bottlenecks, with core value in building integrated platforms for programmable targeted delivery, spatiotemporal smart responsiveness and intrinsic theranostic synergy. Research in this field has evolved from basic molecular discovery to systematic rational design and now clinical smart applications. This review presents a novel research and development roadmap for peptide-metal chelates, elaborating their design principles, structure-function mechanisms and latest biomedical advances. It highlights their unique “Trojan horse” strategy for antibacterial resistance and precise tumor targeting via the EPR effect and tumor microenvironmental triggers such as pH and enzymes. It details their applications in intelligent drug delivery, high-efficacy antimicrobial therapy, precision anticancer treatment, and theranostic platforms integrating imaging and therapy. Addressing gaps in existing fragmented summaries, including the lack of systematic design-synthesis-application integration and insufficient basic-clinical translation analysis, the review also notes unresolved challenges in long-term in vivo safety, bioavailability optimization and GMP-compliant large-scale production. Finally, it prospects core directions like AI-assisted rational molecular design, advanced multi-stimuli responsive materials and multimodal theranostic integration, which are expected to accelerate the clinical translation of peptide-metal chelates and offer innovative solutions for drug-resistant infections and refractory cancers.