Self-Assembled Peptide-GoldNanoparticle 1D NanohybridsFunctionalized with GHK Tripeptide for Enhanced Wound-Healing andPhotothermal Therapy

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.