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Phage-inspired targeting of antibiotic-loaded polymeric micelles for enhanced therapeutic efficacy against monomicrobial sepsis    
Yazarlar (13)
Tülin Özbek
Türkiye
Hatice Demir
Senanur Dokuz
Semra Taşdurmazlı
Türkiye
Utku Özbey
Mehmet Özbil
Türkiye
Murat Topuzoğulları
Türkiye
İrfan Çınar
Türkiye
Doç. Dr. Murat KARAMEŞE Doç. Dr. Murat KARAMEŞE
Kafkas Üniversitesi, Türkiye
Prof. Dr. Selina AKSAK KARAMEŞE Prof. Dr. Selina AKSAK KARAMEŞE
Türkiye
Serap Acar
Türkiye
Ömer Faruk Bayrak
Türkiye
Elif Çadırcı
Türkiye
Devamını Göster
Özet
The rapid increase in bacterial resistance to existing treatments underscores the critical need for novel therapeutic strategies. Here, an innovative approach using targeted nanocarrier systems that mimic phage-bacteria interactions through phage receptor binding protein (Gp45 from the ϕ11 lysogenic phage) or derived peptides (P1, P2, P3, P4, P5), are introduced. These nanodrugs, exhibited receptor-ligand specificity and strong binding affinity, for the first time, were employed for the precise delivery and targeting of antibiotics within living organisms. The actively targeted micelles via two methods were produced; conjugating GP45 to dual antibiotic-loaded PLGA-b-PEG micelles (MiGp45) and the synthesis of peptide-conjugated micelles with dual antibiotic-loaded PLGA-b-PEG-peptide triblock copolymers. The untargeted nano-drug reduced MIC values by 2-10 times for vancomycin and 9-75 times for oxacillin, resulting in a synergistic effect. MiGp45 and MiP1-targeted micelles further reduced MIC values at least twofold, up to ninefold in resistant strains, indicating significant antibacterial improvement. In a mouse model of sepsis by S. aureus, MiGp45 treatment resulted in complete recovery as opposed to death in the untreated group, significantly reduced bacterial load, pro-inflammatory cytokine expression, lung injury, and normalized oxidative stress. The phage-based nanodrugs show tremendous promise as a highly effective antimicrobial treatment targeting multidrug- resistant pathogens.
Anahtar Kelimeler
Phage-based targeting | Dual antibiotic-loaded nanodrug | S. aureus infection | Pneumonia sepsis
Makale Türü Özgün Makale
Makale Alt Türü SSCI, AHCI, SCI, SCI-Exp dergilerinde yayımlanan tam makale
Dergi Adı Journal of Controlled Release
Dergi ISSN 0168-3659 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler SCI-Expanded
Dergi Grubu Q1
Makale Dili Türkçe
Basım Tarihi 04-2025
Cilt No 380
Sayfalar 773 / 786
Doi Numarası 10.1016/j.jconrel.2025.02.035
Makale Linki https://doi.org/10.1016/j.jconrel.2025.02.035