Liposome-Mediated Bacterial Ferroptosis-like Death: A Novel Paradigm for Antimicrobial Therapy

The growing global crisis of antimicrobial resistance (AMR) urgently demands non-classical therapies capable of evading established resistance mechanisms. Bacterial ferroptosis-like death, an iron-dependent process driven by lipid peroxidation, offers a promising strategy to circumvent conventional drug resistance. However, the clinical translation of ferroptosis-like inducers is hindered by poor water solubility and off-target systemic toxicity. Featuring tunable physicochemical characteristics and proven clinical biosafety, liposomes stand out as a viable platform to resolve these translational bottlenecks. Although antibacterial nanomedicines have been extensively investigated, the specific synergies between liposomal engineering and bacterial ferroptosis-like pathways remain underexplored. To bridge this gap, this review systematically delineates the molecular cascades of bacterial ferroptosis-like death and highlights unique mechanistic advantages of liposomes. Importantly, liposome-mediated ferroptosis-like antibacterial therapy faces prominent translational challenges, including biosafety concerns, insufficient stability, and targeting limitations. This review further outlines advanced liposomal engineering strategies to tackle the above obstacles and discusses pressing questions that should be the focus of future ferroptosis-like research. By integrating multidisciplinary research outcomes, this review may provide insights and feasible design guidelines to advance the translational development of liposomal ferroptosis-like inducers against AMR infections.