Tissue nano-transfection of antimicrobial genes drives bacterial biofilm killing in wounds and is potentially mediated by extracellular vesicles

The emergence of bacteria that are resistant to antibiotics is on track to become a major global health crisis. Therefore, there is an urgent need for new treatment options. Here, we studied the implementation of tissue-nanotransfection (TNT) to treat Staphylococcus aureus-infected wounds by deliver...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Journal of controlled release 2024-12, Vol.376, p.1300-1315
Hauptverfasser: Cuellar-Gaviria, Tatiana Z., Rincon-Benavides, Maria Angelica, Halipci Topsakal, Hatice Nur, Salazar-Puerta, Ana Isabel, Jaramillo-Garrido, Shara, Kordowski, Mia, Vasquez-Martinez, Carlos A., Nguyen, Kim Truc, Rima, Xilal Y., Rana, Pranav S.J.B., Combita-Heredia, Orlando, Deng, Binbin, Dathathreya, Kavya, McComb, David W., Reategui, Eduardo, Wozniak, Daniel, Higuita-Castro, Natalia, Gallego-Perez, Daniel
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:The emergence of bacteria that are resistant to antibiotics is on track to become a major global health crisis. Therefore, there is an urgent need for new treatment options. Here, we studied the implementation of tissue-nanotransfection (TNT) to treat Staphylococcus aureus-infected wounds by delivering gene cargos that boost the levels of naturally produced antimicrobial peptides. The Cathelicidin Antimicrobial Peptide gene (CAMP), which produces the antimicrobial peptide LL-37, was used as model gene cargo. In vitro evaluation showed successful transfection and an increase in the transcription and translation of CAMP-coding plasmid in mouse primary epithelial cells. Moreover, we found that the extracellular vesicles (EVs) derived from the transfected cells (in vitro and in vivo) carried significantly higher concentrations of CAMP transcripts and LL-37 peptide compared to control EVs, possibly mediating the trafficking of the antimicrobial contents to other neighboring cells. The TNT platform was then used in vivo on an excisional wound model in mice to nanotransfect the CAMP-coding plasmid on the edge of infected wounds. After 4 days of daily treatment, we observed a significant decrease in the bacterial load in the CAMP-treated group compared to the sham group. Moreover, histological analysis and bacterial load quantification also revealed that TNT of CAMP on S. aureus-infected wounds was effective in treating biofilm progression by reducing the bacterial load. Lastly, we observed a significant increase in macrophage recruitment to the infected tissue, a robust increase in vascularization, as well as and an increased expression of IL10 and Fli1. Our results demonstrate that TNT-based delivery of gene cargos coding for antimicrobial compounds to the wound is a promising approach for combating biofilm infections in wounds. [Display omitted]
ISSN:0168-3659
1873-4995
1873-4995
DOI:10.1016/j.jconrel.2024.10.071