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Hydrogel nanoparticle as an artificial nuclease for selective DNA cleavage

Zhang, Tong LU ; Zhang, Man LU ; Chen, Mingli LU orcid and Ye, Lei LU orcid (2026) In Chemical Engineering Journal 529.
Abstract

Controlled and sequence-selective DNA cleavage plays a crucial role in biomolecular engineering and nucleic acid technologies. Here, we report the development of cerium-coordinated catalytic hydrogel nanoparticles (Ce-CHNP) that exhibit single-strand-selective nuclease activity. Ce-CHNP was synthesized via a one-step polymerization process in which Ce(IV) coordinated with N-hydroxymethyl acrylamide to form nanoceria inside the polymer network. The artificial enzyme exhibits high efficiency for hydrolysis of phosphodiester, with kinetic parameters of Km = 1.20 mM, kcat = 13.57 s−1, and kcat/Km = 1.13 × 104 M−1 s−1 when evaluated using... (More)

Controlled and sequence-selective DNA cleavage plays a crucial role in biomolecular engineering and nucleic acid technologies. Here, we report the development of cerium-coordinated catalytic hydrogel nanoparticles (Ce-CHNP) that exhibit single-strand-selective nuclease activity. Ce-CHNP was synthesized via a one-step polymerization process in which Ce(IV) coordinated with N-hydroxymethyl acrylamide to form nanoceria inside the polymer network. The artificial enzyme exhibits high efficiency for hydrolysis of phosphodiester, with kinetic parameters of Km = 1.20 mM, kcat = 13.57 s−1, and kcat/Km = 1.13 × 104 M−1 s−1 when evaluated using bis(4-nitrophenyl) phosphate as a model substrate. Ce-CHNP also demonstrates excellent stability across a wide pH range and at elevated temperatures. Mechanistic studies, including X-ray photoelectron spectroscopy (XPS), redox assays, and 31P solid-state NMR, elucidated the catalytic mechanism by which Ce(III) and Ce(IV) on nanoceria synergistically hydrolyze phosphodiester bonds. Notably, Ce-CHNP selectively hydrolyzes single-stranded DNA (ssDNA) in the presence of double-stranded DNA (dsDNA). For targeting double stranded DNA (dsDNA) sequences, peptide nucleic acid (PNA)-guided Ce-CHNP system functions as a programmable nuclease to cleave single strand regions generated by PNA invasion. Our results demonstrate that Ce-CHNP offers a programmable artificial nuclease platform useful for nucleic acid processing, and future biosensing, diagnostics and therapeutic applications.

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author
; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Artificial enzymes, Catalytic hydrogel nanoparticles, DNA cleavage, Nanoceria
in
Chemical Engineering Journal
volume
529
article number
173209
publisher
Elsevier
external identifiers
  • scopus:105028038562
ISSN
1385-8947
DOI
10.1016/j.cej.2026.173209
language
English
LU publication?
yes
id
fb283f94-8ae2-4a06-baeb-ac040f4170eb
date added to LUP
2026-02-19 12:06:37
date last changed
2026-05-22 16:21:47
@article{fb283f94-8ae2-4a06-baeb-ac040f4170eb,
  abstract     = {{<p>Controlled and sequence-selective DNA cleavage plays a crucial role in biomolecular engineering and nucleic acid technologies. Here, we report the development of cerium-coordinated catalytic hydrogel nanoparticles (Ce-CHNP) that exhibit single-strand-selective nuclease activity. Ce-CHNP was synthesized via a one-step polymerization process in which Ce(IV) coordinated with N-hydroxymethyl acrylamide to form nanoceria inside the polymer network. The artificial enzyme exhibits high efficiency for hydrolysis of phosphodiester, with kinetic parameters of K<sub>m</sub> = 1.20 mM, k<sub>cat</sub> = 13.57 s<sup>−1</sup>, and k<sub>cat</sub>/K<sub>m</sub> = 1.13 × 10<sup>4</sup> M<sup>−1</sup> s<sup>−1</sup> when evaluated using bis(4-nitrophenyl) phosphate as a model substrate. Ce-CHNP also demonstrates excellent stability across a wide pH range and at elevated temperatures. Mechanistic studies, including X-ray photoelectron spectroscopy (XPS), redox assays, and <sup>31</sup>P solid-state NMR, elucidated the catalytic mechanism by which Ce(III) and Ce(IV) on nanoceria synergistically hydrolyze phosphodiester bonds. Notably, Ce-CHNP selectively hydrolyzes single-stranded DNA (ssDNA) in the presence of double-stranded DNA (dsDNA). For targeting double stranded DNA (dsDNA) sequences, peptide nucleic acid (PNA)-guided Ce-CHNP system functions as a programmable nuclease to cleave single strand regions generated by PNA invasion. Our results demonstrate that Ce-CHNP offers a programmable artificial nuclease platform useful for nucleic acid processing, and future biosensing, diagnostics and therapeutic applications.</p>}},
  author       = {{Zhang, Tong and Zhang, Man and Chen, Mingli and Ye, Lei}},
  issn         = {{1385-8947}},
  keywords     = {{Artificial enzymes; Catalytic hydrogel nanoparticles; DNA cleavage; Nanoceria}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Chemical Engineering Journal}},
  title        = {{Hydrogel nanoparticle as an artificial nuclease for selective DNA cleavage}},
  url          = {{http://dx.doi.org/10.1016/j.cej.2026.173209}},
  doi          = {{10.1016/j.cej.2026.173209}},
  volume       = {{529}},
  year         = {{2026}},
}