Antimicrobial peptides in anti-infective and immunomodulatory applications: Mechanisms, challenges, and emerging...

Antimicrobial Peptides (AMPs) evolutionarily conserved effectors of innate immunity, have emerged as multifunctional agents with broad-spectrum antimicrobial activity, immunomodulatory capabilities, and potential applicability in cancer therapy. Despite their functional diversity and biological potency, the clinical translation of AMPs remains constrained by significant challenges, including proteolytic instability, hemolytic toxicity, high production costs, and protracted development pipelines. This review examines how the diverse molecular mechanisms through which AMPs exert antimicrobial effects-including membrane disruption, intracellular targeting, and immunomodulation-are intrinsically linked to their structural diversity and ecological breadth. We critically evaluate engineering strategies that improve developability, including rational sequence modification, nano/targeted delivery, optimized formulations, and combination regimens with antibiotics or bacteriophages. As a complementary perspective, we briefly summarize recent progress in computational prediction and AI-driven screening/design for AMP discovery and multi-objective optimization, while highlighting major limitations such as dataset bias, scarcity of reliable negative data, and experimental validation bottlenecks. Beyond infectious disease, we discuss the impact of AMPs on reshaping the tumor microbiota-immune axis, revealing a dual function in both microbial control and immune regulation within oncogenic contexts. Overall, this review provides a balanced appraisal of evidence and translational pathways for advancing AMP-based therapeutics.