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PEGylation of silver nanoparticles by physisorption of cyclic poly(ethylene glycol) for enhanced dispersion stability, antimicrobial activity, and cytotoxicity.

ABSTRACT: Silver nanoparticles (AgNPs) are practically valuable in biological applications. However, no steady PEGylation has been established, which is essential for internal use in humans or animals. In this study, cyclic PEG (c-PEG) without any chemical inhomogeneity is physisorbed onto AgNPs to successfully PEGylate and drastically enhance the dispersion stability against physiological conditions, white light, and high temperature. In contrast, linear HO-PEG-OH and MeO-PEG-OMe do not confer stability to AgNPs, and HS-PEG-OMe, which is often used for gold nanoparticles, sulfidates the surface to considerably degrade the properties. TEM shows an essentially intact nanostructure of c-PEG-physisorbed AgNPs even after heating at 95 °C, while complete disturbance is observed for other AgNPs. Molecular weight- and concentration-dependent stabilization by c-PEG is investigated, and DLS and ζ-potential measurements prove the formation of a c-PEG layer on the surface of AgNPs. Furthermore, c-PEG-physisorbed AgNPs exhibit persistent antimicrobial activity and cytotoxicity.

SUBMITTER: Oziri OJ

PROVIDER: S-EPMC9417676 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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PEGylation of silver nanoparticles by physisorption of cyclic poly(ethylene glycol) for enhanced dispersion stability, antimicrobial activity, and cytotoxicity.

Oziri Onyinyechukwu Justina OJ Wang Yubo Y Watanabe Tomohisa T Uno Shuya S Maeki Masatoshi M Tokeshi Manabu M Isono Takuya T Tajima Kenji K Satoh Toshifumi T Sato Shin-Ichiro SI Miura Yutaka Y Yamamoto Takuya T

Nanoscale advances 20211112 2

Silver nanoparticles (AgNPs) are practically valuable in biological applications. However, no steady PEGylation has been established, which is essential for internal use in humans or animals. In this study, cyclic PEG (<i>c</i>-PEG) without any chemical inhomogeneity is physisorbed onto AgNPs to successfully PEGylate and drastically enhance the dispersion stability against physiological conditions, white light, and high temperature. In contrast, linear HO-PEG-OH and MeO-PEG-OMe do not confer sta ...[more]

PMID: 36132700

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Project description:Conjugating antimicrobial peptides (AMPs) to nonlinear polymers is a promising strategy to overcome the translational challenges of AMPs toward treating infections caused by antibiotic-resistant bacteria. Nonlinear polymers, and therefore conjugates, can be prepared with various architectures (e.g., star-shaped, comb-like, hyperbranched, etc.), however, the effects of polymer architecture on antimicrobial performance and related properties, like size and morphology in solution and secondary structure, are not yet well-understood. Here, we compare conjugates of the human chemokine-derived AMP stapled P9 with poly(ethylene glycol) (PEG) prepared in two of the major nonlinear architectures: star-shaped and comb-like. At comparable molecular weights and compositions (peptide wt %), comb-like conjugates afford increased helicity, solubility, antimicrobial activity, and proteolytic stability compared to star-shaped analogs. We then leveraged the expansive design space of comb-like architectures to prepare conjugates with different backbone lengths and PEG side chain lengths, with shorter PEG side chains leading to increased helicity, yet potentially less shielding from proteolytic degradation and the longest backbone lengths furnishing the most potent antimicrobial activity. Both comb-like and star-shaped conjugates display high zeta potential, indicating that the cationic AMPs were accessible for electrostatic interactions with bacterial membranes. Yet, the comb-like conjugates showed a higher fraction of unimolecular structures indicative of a lower propensity for supramolecular assembly that could be encumbering the desired AMP-bacteria interactions in the star-shaped conjugates. Together, our work shows comb-like AMP-polymer conjugates to outperform analogous star-shaped conjugates, while adding design flexibility to access an expansive range of monomer chemistries, monomer distributions, and backbone lengths to modulate performance-determining properties and ultimately furnish an effective suite of AMP-polymer materials as alternatives to conventional antibiotics for combatting bacterial infections.

Project description:Antimicrobial peptides (AMPs) are promising alternatives to conventional antibiotics for treating infections caused by drug-resistant bacteria; yet, many peptides are limited by toxicity to eukaryotic cells and instability in biological environments. Conjugation to linear polymers that reduce cytotoxicity and improve stability, however, often decreases antimicrobial activity. In this work, we combine the biocompatibility advantages of poly(ethylene glycol) (PEG) with the efficacy merits of nonlinear polymer architectures that accommodate multiple AMPs per molecule. By conjugating a chemokine-derived AMP, stapled Ac-P9, to linear and star-shaped PEG with various arm numbers and lengths, we investigated the role of molecular architecture in solution properties (i.e., ζ-potential, size, and morphology) and performance (i.e., antimicrobial activity, hemolysis, and protease resistance). Linear, 4-arm, and 8-arm conjugates with 2-2.5 kDa PEG arms were found to form nanoscale structures in solution with lower ζ-potentials relative to the unconjugated AMP, suggesting that the polymer partially shields the cationic AMP. Reducing the length of the PEG arms of the 8-arm conjugate to 1.25 kDa appeared to better reveal the peptide, seen by the increased ζ-potential, and promote assembly into particles with a larger size and defined spherical morphology. The antimicrobial effects exerted by the short 8-arm conjugate rivaled that of the unconjugated peptide, and the AMP constituents of the short 8-arm conjugate were protected from proteolytic degradation. All other conjugates examined also imparted a degree of protease resistance, but exhibited some reduced level of antimicrobial activity as compared to the AMP alone. None of the conjugates caused significant cytotoxic effects, which bodes well for their future potential to treat infections. While enhancing proteolytic stability often comes with the cost of lower antimicrobial activity, we have found that presenting AMPs at high density on a neutral nonlinear polymer strikes a favorable balance, exhibiting both enhanced stability and high antimicrobial activity.

Dataset Information

PEGylation of silver nanoparticles by physisorption of cyclic poly(ethylene glycol) for enhanced dispersion stability, antimicrobial activity, and cytotoxicity.

Publications

PEGylation of silver nanoparticles by physisorption of cyclic poly(ethylene glycol) for enhanced dispersion stability, antimicrobial activity, and cytotoxicity.

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