Bioactive Peptide Nano-assemblies with pH-Triggered Shape Transformation for Antibacterial Therapy

Peptide-based supramolecular nano-assemblies have received much attention due to their importance in drug delivery, therapeutics, and tissue regeneration. Recent developments in dynamic self-assembly have shifted the emphasis toward producing novel nanostructures with stimuli-responsive assembly behavior. Here, we report the fabrication of a bio-nano construct with dual functionality and environmental tunability, offering advancements in wound healing applications. In particular, we have utilized a collagen-inspired peptide amphiphile to fabricate spherical nanoparticles via nanoprecipitation and explored its unique intrinsic stimuli-responsive self-assembling property to encapsulate and release the hydrophobic drug, ferulic acid. The peptide-based spherical nanoparticles demonstrated a dynamic behavior and a shape transition into nanofibers when exposed to the basic chronic wound environment, triggering the release of the encapsulated ferulic acid. The structural transformation of the nanoparticles into the nanofibers provided an advanced synthetic scaffold for wound closure, while the released ferulic acid provided assistance in combating microbial infection to offer a dual advantage of the nano construct. Interestingly, the novel nanocarrier demonstrated an enhanced efficacy in the bactericidal effect offered by ferulic acid. Such transmorphic behavior of the peptide could be used for constructing stimuli-responsive nano-assemblies for overcoming the limitations of hydrophobic drugs in therapeutics.