Stimuli-Responsive Smart Nanocarriers Targeting Resistance Genes in Carbapenem-Resistant Enterobacteriaceae
Abstract
Carbapenem-resistant Enterobacteriaceae (CRE) are among the most urgent antimicrobial resistance threats due to the widespread dissemination of mobile carbapenemase genes (e.g., blaNDM, blaKPC, blaOXA-48, blaVIM) and the resulting failure of last-line β-lactam therapies. This work presents a stimuli-responsive smart nanocarrier platform engineered for infection-site–triggered release and intracellular delivery of gene-silencing payloads targeting carbapenem resistance determinants. Biodegradable polymeric nanoparticles were formulated by nanoprecipitation and functionalized to enhance bacterial association while maintaining colloidal stability. Particles exhibited nanoscale size (145 ± 12 nm), narrow dispersity, and high encapsulation efficiency (>80%). In vitro release studies demonstrated accelerated cargo release under acidic conditions representative of infected microenvironments (pH 5.5) compared with physiological pH (7.4). Across three CRE clinical isolates, smart nanocarrier treatment produced substantial growth inhibition and a marked reduction in bacterial burden (~4.6–5.4 log10 decrease versus baseline), accompanied by significant downregulation of resistance-gene expression measured by qPCR. Cytotoxicity testing in mammalian cells showed high viability at therapeutically relevant nanocarrier concentrations. Collectively, these results support stimuli-responsive gene-targeted nanocarriers as a promising precision strategy to mitigate CRE resistance mechanisms.
How to Cite
Shalini Saini, "Stimuli-Responsive Smart Nanocarriers Targeting Resistance Genes in Carbapenem-Resistant Enterobacteriaceae", Vol. 3, Issue 3, 06-06-2025, pp. 80-92.
