Controlled self-assembly of macrocyclic peptide into multifunctional photoluminescent nanoparticles

J Pharm Sci. 2025 Feb;114(2):990-1001. doi: 10.1016/j.xphs.2024.11.006. Epub 2024 Nov 16.

Abstract

Self-assembled peptide nanoparticles are unique stimuli responsive biodegradable materials with applications in biomedicines as delivery carriers and imaging agents. This study investigates the controlled self-assembly of chicken Angiogenin 4 derived immunomodulatory macrocyclic peptide (mCA4-5) in the presence of an inert amphipathic stabilizing peptide and as a function of pH, temperature and presence of ions to yield optically active, physiologically stable and biodegradable peptide nanoparticles. The photoluminescent peptide nanoparticles (PLPNs) produced were characterized for the size, surface charge, optical properties and crystallinity. The carvacrol loaded nanoparticles prepared by facile encapsulation of the drug during the self-assembly process were evaluated for the drug release efficacies, as a function of pH and in the presence of reducing agent. Carvacrol loaded, physiologically stable PLPNs obtained with high conversion efficacy were highly effective against planktonic bacteria and bacterial biofilms and efficiently eradicated intracellular bacteria in infected macrophages and fibroblast. Furthermore, the drug-loaded nanoparticles exhibited significant antioxidant activities and immunomodulatory effects, highlighting their multifunctional therapeutic potential.

Keywords: Antimicrobial; Drug delivery; Immunomodulatory; Peptide self assembly; Photoluminescent nanoparticles.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Antioxidants / administration & dosage
  • Antioxidants / chemistry
  • Antioxidants / pharmacology
  • Biofilms / drug effects
  • Chickens
  • Cymenes / chemistry
  • Cymenes / pharmacology
  • Drug Carriers / chemistry
  • Drug Liberation
  • Fibroblasts / drug effects
  • Hydrogen-Ion Concentration
  • Macrophages / drug effects
  • Macrophages / microbiology
  • Mice
  • Nanoparticles* / chemistry
  • Particle Size
  • Peptides* / chemistry
  • Peptides, Cyclic* / chemistry
  • RAW 264.7 Cells
  • Ribonuclease, Pancreatic / chemistry

Substances

  • carvacrol
  • Cymenes
  • Antioxidants
  • Peptides, Cyclic
  • Drug Carriers
  • Anti-Bacterial Agents
  • Ribonuclease, Pancreatic
  • Peptides
  • angiogenin