Photothermally Active Cryogel Devices for Effective Release of Antimicrobial Peptides: On-Demand Treatment of Infections

ACS Appl Mater Interfaces. 2020 Dec 23;12(51):56805-56814. doi: 10.1021/acsami.0c17633. Epub 2020 Dec 8.

Abstract

There has been significant interest in the use of peptides as antimicrobial agents, and peptide containing hydrogels have been proposed as biological scaffolds for various applications. Limited stability and rapid clearance of small molecular weight peptides pose challenges to their widespread implementation. As a common approach, antibacterial peptides are physically loaded into hydrogel scaffolds, which leads to continuous release through the passive mode with spatial control but provides limited control over drug dosage. Although utilization of peptide covalent linkage onto hydrogels addresses partially this problem, the peptide release is commonly too slow. To alleviate these challenges, in this work, maleimide-modified antimicrobial peptides are covalently conjugated onto furan-based cryogel (CG) scaffolds via the Diels-Alder cycloaddition at room temperature. The furan group offers a handle for specific loading of the peptides, thus minimizing passive and burst drug release. The porous nature of the CG matrix provides rapid loading and release of therapeutic peptides, apart from high water uptake. Interfacing the peptide adduct containing a CG matrix with a reduced graphene oxide-modified Kapton substrate allows "on-demand" photothermal heating upon near-infrared (NIR) irradiation. A fabricated photothermal device enables tunable and efficient peptide release through NIR exposure to kill bacteria. Apart from spatial confinement offered by this CG-based bandage, the selective ablation of planktonic Staphylococcus aureus is demonstrated. It can be envisioned that this modular "on-demand" peptide-releasing device can be also employed for other topical applications by appropriate choice of therapeutic peptides.

Keywords: Diels−Alder reaction; S. aureus; antimicrobial peptide; cryogel; photothermal.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Antimicrobial Cationic Peptides / chemistry
  • Antimicrobial Cationic Peptides / pharmacology*
  • Cryogels / chemical synthesis
  • Cryogels / chemistry*
  • Cryogels / radiation effects
  • Cycloaddition Reaction
  • Drug Liberation
  • Escherichia coli / drug effects
  • Furans / chemical synthesis
  • Furans / chemistry
  • Furans / radiation effects
  • HeLa Cells
  • Heating
  • Humans
  • Infrared Rays
  • Methacrylates / chemical synthesis
  • Methacrylates / chemistry
  • Methacrylates / radiation effects
  • Microbial Sensitivity Tests
  • Polyethylene Glycols / chemical synthesis
  • Polyethylene Glycols / chemistry
  • Polyethylene Glycols / radiation effects
  • Staphylococcal Infections / drug therapy*
  • Staphylococcus aureus / drug effects

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Cryogels
  • Furans
  • Methacrylates
  • polyethylene glycol methacrylate
  • Polyethylene Glycols