Engineering hydrophobic and electrostatic interactions for selective inactivation of bacteriophages by mixed-ligand nanoparticles

Abstract

Bacteriophage contamination poses significant challenges in bacteria-based industries, disrupting processes that rely on bacterial metabolism, such as insulin production using Escherichia coli. This study introduces mixed-ligand nanoparticles (MLNPs) as a novel solution for selective phage inactivation while preserving bacterial viability. By controlling the ratios of positively charged ((11-mercaptoundecyl)-N,N,N-trimethylammonium cation, TMA), negatively charged (mercaptoundecanate anion, MUA), and hydrophobic (dodecane-1-thiol, DDT) ligands, MLNPs leverage tailored multivalent interactions to disrupt bacteriophage functions. The optimum MLNP formulation (60:22:18 ratio of TMA:MUA:DDT) achieved complete phage inactivation (7 log reduction) within 9 hours at 25 °C, a significant improvement over traditional methods that require harsh conditions, elevated temperatures, and/or extended durations. Our results demonstrate that hydrophobic ligands enhance phage inactivation while maintaining bacterial viability, with survival rates exceeding 90%. The MLNPs were tested against diverse bacteriophages, including MS2, M13, Qβ, LR1_PA01, and vB_SauS_CS1, achieving broad-spectrum efficacy without causing significant harm to host bacteria. Furthermore, cytotoxicity tests on mammalian 3T3 NIH fibroblast cells confirmed the high biocompatibility of MLNPs, with cell viability exceeding 90% at effective concentrations. This study highlights the potential of MLNPs as a selective and cost-effective tool for managing bacteriophage contamination, offering advantages for industrial and medical applications by ensuring bacterial productivity while mitigating phage-induced disruptions.

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Article information

Article type
Paper
Submitted
11 Feb 2025
Accepted
21 Apr 2025
First published
24 Apr 2025
This article is Open Access
Creative Commons BY license

Nanoscale, 2025, Accepted Manuscript

Engineering hydrophobic and electrostatic interactions for selective inactivation of bacteriophages by mixed-ligand nanoparticles

S. Raza, P. Mente, B. Kamiński, B. Bończak, H. Maleki-Ghaleh, V. Vignesh and J. Paczesny, Nanoscale, 2025, Accepted Manuscript , DOI: 10.1039/D5NR00612K

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