ArticleJournal of nanobiotechnology2026
Design and evaluation of a bifunctional fusion polypeptide for targeted delivery of tigecycline against drug-resistant Klebsiella pneumoniae.
Article in Journal of nanobiotechnology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
The overuse of antibiotics and the continuous evolution of drug-resistant bacteria present substantial obstacles to the clinical treatment of Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections. This study reports the rational design of a bifunctional fusion polypeptide, S-thanatin (Ts)-functionalized elastin-like carrier (Ts-ELP), which integrates the antimicrobial peptide (AMP) Ts with a human-derived elastin‑like polypeptides (ELPs). This designer polypeptide serves as a smart carrier, capable of efficiently encapsulating the broad-spectrum antibiotic tigecycline (Tig) via reversible temperature-responsive phase transition hydrophobic interaction, resulting in a self-assembled, targeted nano-antibiotic, Tig@Ts-ELP (Tig@TsE). Comprehensive in vitro and in vivo evaluations demonstrate that Tig@TsE exhibits multiple advantageous features, including rapid and simple preparation, specific lipopolysaccharide (LPS)-targeting capability, excellent in vivo targeted delivery efficiency, and dual-responsive drug release triggered by the acidic pH and elevated matrix metalloproteinase-9 (MMP-9) levels in the CRKP-infected microenvironment, coupled with favorable biocompatibility. Moreover, the Ts peptide and Tig exhibit marked synergistic antibacterial effects against CRKP. This innovative nano-antibiotic delivery system is designed to increase local drug concentration at the infection site, boost bactericidal activity, and reduce systemic toxicity, thereby presenting a promising therapeutic strategy for the treatment of drug-resistant bacterial pneumonia.
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