Synthetically designed peptide-based biomaterials with stimuli-responsive and membrane-active properties for biomedical applications

Peptide-based biomaterials have been extensively investigated for biomedical applications due to their high structural and functional versatility. Particularly, peptides that can respond to different stimuli, such as pH, redox potential, temperature, light, and enzymes can offer controllable actions in target body locations. Therefore, smart, multifunctional peptide-based nanoparticle (NP) systems that respond to pathological stimuli with the ability to facilitate cellular internalization and enhance cytosolic release via disrupting membranes are of great interest in biomaterials research. This review predominantly focuses on synthetically designed stimuli-responsive peptides that serve different biomedical applications, with emphasis on drug and gene delivery, and touches upon recent advances in membrane-active peptide NPs for enhanced therapeutic activity. The review also provides an outlook on future directions on the maturing field of peptide-based therapeutics.