Antibacterial Photodynamic Gold Nanoparticles for Skin Infection

Abstract

Damage or injury to the skin creates wounds that are vulnerable to bacterial infection, which in turn retards the process of skin regeneration and wound healing. In patients with severe burns and those with chronic diseases, such as diabetes, skin infection by multidrug-resistant bacteria can be lethal. Therefore, a broad-spectrum therapy to effectively eradicate bacterial infection through a mechanism different from that of antibiotics is much sought after. We successfully synthesized antibacterial photodynamic gold nanoparticles (AP-AuNPs), which are self-assembled nanocomposites of an antibacterial photodynamic peptide and poly­(ethylene glycol) (PEG)-stabilized AuNPs. The AP-AuNPs exhibited aqueous and light stability, a satisfactory generation of reactive oxygen species (ROS), and a remarkable antibacterial effect toward both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli upon light irradiation. Moreover, the synthesized nanocomposites significantly inhibited bacterial growth and biofilm formation in vitro. Photodynamic antibacterial treatment accelerated the wound-healing rate in S. aureus infections, mimicking staphylococcal skin infections. Using a combination of the bactericidal effect of a peptide, the photodynamic effect of a photosensitizer, and the multivalency clustering on AuNPs for maximal antibacterial effect under light irradiation, we synthesized AP-AuNPs as a wound-dressing nanomaterial in skin infections to promote wound healing. Our findings indicate a promising strategy in the management of bacterial infections resulting from damaged skin tissue, an aspect that has not been fully explored by our peers.

Use of Photodynamic Therapy Associated with Antimicrobial Peptides for Bacterial Control: A Systematic Review and Meta-Analysis

“…The results of the systematic review show that all articles had an in vitro experimental design and 3 of them were both in vitro and in vivo experimental studies [ 28 , 30 , 31 ]. Moreover, of the 20 articles analyzed, 18 performed the therapy with a portion of the PS redirected to AMP and only 2 studies performed the therapy combined with AMP [ 12 , 13 ].…”

“…The shortest and longest irradiation times were 30 s [ 14 ] and 20 h [ 21 , 22 ], respectively. The most commonly used PS were chlorin e6 [ 12 , 13 , 24 , 28 , 30 , 31 ] and porphyrin [ 14 , 16 , 17 , 19 , 21 , 22 , 25 , 26 ]. Additionally, the most frequently used microorganism in the assay was Staphylococcus aureus [ 12 , 14 , 15 , 17 , 18 , 19 , 20 , 21 , 22 , 24 , 26 , 27 , 29 , 30 , 31 ], followed by Escherichia coli [ 12 , 14 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 26 , 27 , 30 , 31 ].…”

“…To overcome this limitation, aPDT associated with enzymes or antifungal agents was more effective for microbial inactivation than aPDT alone [ 5 , 9 ]. Additionally, antimicrobial peptides (AMP) have been used alone [ 10 , 11 ], combined with aPDT [ 12 , 13 ], or by conjugating a PS to the AMP molecule [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ], presenting satisfactory results in pathogenic microorganism inactivation.…”

Nanomaterials in Skin Regeneration and Rejuvenation

“…This was traditionally achieved by the addition of conventional antibiotics (such as sulfadiazine, whose properties have been addressed in a dedicated section, vide infra), but with the advent of nanomaterials this role has been taken by metal or metal-based nanoparticles (such as gold [71], silver [59][60][61], copper, zinc oxide, copper oxide or sulphide [54,62,63]. Metal nanoparticles (e.g., AuNPs and AgNPs) exert their antimicrobial activity by a series of mechanisms involving direct interaction with the negatively charged bacterial cell membrane, its disruption, and subsequent leakage of the inner cellular material [51].…”

Nanodot-doped peptide hydrogels for antibacterial phototherapy and wound healing

“…Antimicrobial peptides (AMPs) are also a powerful weapon against multidrug resistance in the “post-antibiotic era”. 23–26 Their unique mechanism of membrane destruction often makes them broad-spectrum antimicrobials, and as the membrane is so essential for bacterial cells, resistance development will be relatively rare. Therefore, we speculate that the combination of low temperature photothermal and photodynamic therapy with antimicrobial peptides may achieve an added effect of “1 + 1 > 2”, that is the former reduces the viability of bacterial cells and opens a gap in the biofilm, while the latter carries out physical infiltration for the final effective harvest.…”