Self-Assembled Peptide-Gold Nanoparticle 1D Nanohybrids Functionalized with GHK Tripeptide for Enhanced Wound-Healing and Photothermal Therapy

Abstract

Glycyl-l-histidyl-l-lysine (GHK) tripeptides are known for their remarkable therapeutic potential, including wound-healing, anti-inflammatory activity, and cellular regeneration. However, their clinical application has been significantly hindered by poor biological stability and limited efficacy in a physiological medium. In this study, we introduce a sophisticated approach to overcome these limitations by developing supramolecular peptide nanofiber-gold (Au) nanoparticle (NP) hybrids functionalized with GHK tripeptides. By strategically manipulating peptide self-assembly and NP integration, we demonstrated a useful platform that enhances both therapeutic efficacy and material stability. Our methodology involves the precise engineering of 9-fluorenylmethoxycarbonyl-diphenylalanine scaffolds with GHK and KHG tripeptides, enabling robust nanofibril formation through π-π stacking and hydrogen bonding. Critically, we discovered that the specific amino acid sequence significantly influences the surface exposure of lysine, directly impacting the nanohybrid’s wound-healing capabilities. The resultant nanohybrids exhibit exceptional characteristics: Au NPs are spatially confined within the peptide nanofibers, achieving a remarkably uniform size distribution of approximately 3 nm. These nanohybrids demonstrate superior near-infrared (NIR) light absorption and photothermal conversion efficiency, enabling effective eradication of cancer cells and organoids killing under NIR irradiation. This dual-functional nanohybrid integrates biocompatible and enzymatically degradable peptide scaffolds to achieve synergistic wound-healing and cancer-killing effects. By mitigating the cytotoxicity and biodegradability issues associated with conventional photothermal agents, our system provides a promising strategy to improve postoperative cancer therapy and promote tissue regeneration. This work highlights the potential of peptide-inorganic nanohybrids in advancing multifunctional therapeutic platforms for cancer treatment and tissue repair. © 2025 American Chemical Society.