Peptide‐based antibacterial nanoplatforms: Design principles, stimuli‐regulated behaviors, and applications

Abstract

The increasing prevalence of multidrug‐resistant bacterial infections has highlighted the limitations of conventional antibiotics and accelerated the development of alternative antimicrobial strategies. Antimicrobial peptides exhibit broad‐spectrum activity and low resistance propensity; however, their clinical translation is hindered by poor stability, rapid degradation, and limited controllability in complex physiological environments. In this context, peptide‐based responsive materials and functional nanoplatforms have emerged as a powerful materials‐oriented strategy to overcome these challenges. This review systematically summarizes recent advances in peptide‐based antibacterial nanoplatforms, covering multiple design dimensions including self‐assembled peptide nanomaterials, inorganic hybrid systems, polymer‐based platforms, and lipid‐based nanocarriers. We highlight peptide self‐assembly strategies based on amino acids, short peptides, peptide amphiphiles, and unnatural amino acids, emphasizing supramolecular chemistry and sequence‐dependent structural regulation. Representative hybrid systems including peptide–metal (Ag, Au), mesoporous silica, organosilica, and MXene platforms, as well as polymeric (PAMAM, polysaccharide, PLGA) and lipid systems (liposomes, solid lipid nanoparticles, nanostructured lipid carriers, self‐emulsifying drug delivery systems), are discussed in terms of antibacterial mechanisms, delivery enhancement, and environmental responsiveness. Furthermore, we summarize biointerface engineering strategies, including PEGylation, cell‐penetrating peptides, and chitosan modification, together with optimization of peptide building blocks via natural sequence engineering, hybrid peptide design, and de novo amphiphilic sequence construction. Importantly, we highlight microenvironment‐responsive regulation strategies, including protease inhibition and permeability enhancement, as well as stimulus‐responsive behaviors triggered by enzymatic, chemical, or interfacial cues. Emerging systems such as self‐propelled micro/nanomotors are also introduced. Finally, we discuss current challenges and future perspectives in developing intelligent, adaptive, and stimuli‐responsive peptide‐based antibacterial nanoplatforms, with particular emphasis on their potential to address infection control and antimicrobial resistance in animal health and livestock production systems.