Cell-based and cell-inspired strategies emerge as potent tools against antimicrobial resistance

The escalating crisis of Antimicrobial Resistance (AMR) poses a severe global health threat, particularly for vulnerable populations like immunocompromised cancer patients. Conventional antibiotics are increasingly limited by issues such as microbial dysbiosis, systemic toxicity, poor tissue penetration, biofilm protection, and intracellular bacterial persistence. This necessitates the development of novel approaches that can overcome these physiological and microbial barriers, leading to the exploration of advanced cellular and biomimetic strategies.

This comprehensive review systematically classified emerging cell-based and cell-inspired anti-infective strategies, organizing them by the therapeutic role of their cellular components. The authors analyzed approaches where viable cells act as living medicines, cells function as carriers for antimicrobial payloads, and methods involving in vivo host-cell modulation. Additionally, the review discussed cell-derived and biomimetic platforms, such as extracellular vesicles and membrane-coated nanoparticles. The therapeutic mechanisms of these diverse strategies were thoroughly examined, focusing on infection-site targeting, pathogen eradication, immune regulation, and post-infectious tissue recovery.

The review identified three primary categories of cell-based strategies. First, viable cells act as living medicines, leveraging intrinsic or engineered functions like inflammatory homing, pathogen recognition, phagocytosis, reactive oxygen and nitrogen species generation, antimicrobial peptide secretion, neutrophil extracellular trap formation, and infected-cell killing to enhance bacterial clearance. Second, cells serve as carriers for antimicrobial payloads, including antibiotics, photosensitizers, nanomedicines, and immunomodulators, thereby improving lesion targeting, barrier traversal, local retention, and controlled release. Third, in vivo host-cell modulation restores or reprograms endogenous immune cells through gene delivery, immune regulation, intracellular infection control, or cell hitchhiking, enhancing host antibacterial defense without ex vivo manufacturing. > Beyond live cells, cell-derived and biomimetic platforms, including extracellular vesicles, membrane-coated nanoparticles, and artificial cells, reproduce selected cellular functions such as targeting, immune evasion, toxin neutralization, pathogen capture, and chemical antibacterial activity. These strategies collectively target infection-site localization, direct pathogen eradication, immune system modulation, and facilitate post-infectious tissue recovery.