Synthesis of Hydrogen-Bonded Organic Framework Nanoenzyme for Targeting Antibacterial Applications

doi:10.19894/j.issn.1000-0518.250378

Chinese Journal of Applied Chemistry ›› 2026, Vol. 43 ›› Issue (2): 195-207.DOI: 10.19894/j.issn.1000-0518.250378

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Synthesis of Hydrogen-Bonded Organic Framework Nanoenzyme for Targeting Antibacterial Applications

Li CHEN¹^,², Chuan-Qi ZHAO¹^,²()

^1.Interdisciplinary Laboratory for Frontier Chemistry，Changchun Institute of Applied Chemistry，Chinese Academy of Sciences，Changchun 130022，China
^2.School of Applied Chemistry and Engineering，University of Science and Technology of China，Hefei 230026，China

Received:2025-10-03 Accepted:2025-12-01 Published:2026-02-01 Online:2026-03-06
Contact: Chuan-Qi ZHAO
About author:zhaocq@ciac.ac.cn
Supported by:
Jilin Provincial Natural Science Foundation(20210101130JC);the National Nature Science Foundation of China(22377120);the National Key R&D Program of China(2022YFA1205804)

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Abstract

Abstract:

Bacterial infection poses a significant hazard to public health and life. Antibiotic therapy can readily result in multidrug resistance. Despite significant efforts to enhance the effectiveness of current antibiotics or create new ones， bacteria's innate capacity to develop resistance has outpaced the rate of antibiotic development. This suggests that attempts to create sustainable antimicrobial treatments are ultimately destined to be unsuccessful. Herein， a selective therapeutic HOFzyme （Pro@HOF@apt-Cu） based on DNA-templated ultrasmall CuNPs grafted on peroxidase-mimicking FeTCPP-based HOF targeting lipopolysaccharide （LPS） is presented. FeTCPP-based HOF exhibit excellent POD-like activity， being not only able to catalyze the generation of more toxic hydroxyl radicals from H₂O₂ in the infection-rich microenvironment to disrupt the bacterial periplasm， but also able to oxidize surface Cu（0） to Cu（Ⅰ）， thus boosting the bioorthogonal catalytic activity. The conjugation of the HOF with aptamer allows for active targeting of LPS on the surface of gram-negative bacteria. The antibacterial action of these HOFzymes is observably more significant than non-targeted treatment. Moreover， the inherent pores of HOF facilitated the loading of prodrugs， which realized effective drug delivery and in situ synthesis， greatly reduced off-target toxicity and enhanced therapeutic effects. Overall， this synergistic therapeutic strategy shows promising potential as a future treatment for infections caused by gram-negative bacteria.

Key words: Hydrogen-bonded organic framework, Bioorthogonal, Nanozyme, Antibacterial applications

CLC Number:

O614

Li CHEN, Chuan-Qi ZHAO. Synthesis of Hydrogen-Bonded Organic Framework Nanoenzyme for Targeting Antibacterial Applications[J]. Chinese Journal of Applied Chemistry, 2026, 43(2): 195-207.

Figures/Tables 7

Table 1 Oligonucleotids used in the experiment

Name	Sequence
NH₂（CH₂）₆-Linker	NH₂（CH₂）₆-CAACATCATCAACAC
Linker-T30-LPS	GTTGTAGTAGTTGTGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCCTTCTAACAGAATGTTGTTAGATAGC
Linker-T30-LPS-FAM	GTTGTAGTAGTTGTGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTCCTTCTAACAGAATGTTGTTAGATAGC-FAM
Linker-T30-WA	GTTGTAGTAGTTGTGTTTTTTTTTTTTTTTTTTTTTTTTTTTTTT

Fig.1 （A） SEM image of Pro@HOF@apt-Cu （scale bar， 300 nm）；（B） Zeta potential of HOF， Pro@HOF， HOF@apt-Cu and Pro@HOF@apt-Cu；（C） DLS curves of Pro@HOF@apt-Cu， Pro@HOF and HOF；（D） PXRD patterns of Pro@HOF@apt-Cu， HOF@apt-Cu and HOF；（E） FT-IR specta of Pro@HOF@apt-Cu and HOF；（F） Fluorescence spectra of Pro@HOF and Pro@HOF@apt-Cu-FAM

Fig.2 （A） Absorbance of TMB solution with different times；（B） Michaelis-Menten fitting and （C） the associated Lineweaver-Burk fitting curves of HOF@apt-Cu （20 μg/mL）；（D） Schematic representation of the bioorthogonal generation of dyes in solution；（E） Fluorescence spectra of the HOF@apt-Cu-catalyzed CuAAC reaction in water. The spectra were obtained by introducing HOF@apt-Cu and HOF@apt-Cu+H2O2 to samples 1 and 2， respectively， and allowing them to react for 30 min

Fig.3 Survival rates of E.coli （A） and S.aureus （B） corresponding to （C） bacterial colonies on agar plates；（C） Photos of bacterial colonies consisting of S.aureus and E.coli after different treatments；（D） SEM images of S.aureus and E.coli samples after different treatments

Fig.4 Crystal violet-stained biofilm biomass determined by measuring OD590 （A） and related crystal violet staining pictures （B） treated with different groups：（1） Control，（2） Pro@HOF@apt-Cu，（3） HOF@apt-Cu，（4） Pro@HOF+H2O2，（5） Pro@HOF@apt-Cu+H2O2；（C） Live/dead staining images of biofilms， scale bar， 100 μm；（D） 3D CLSM pictures of biofilms under various treatment settings

Fig.5 （A） Pictures of mice and （B） magnification photographs of mice after different treatments；（C） Histology images of the wound tissue at the implanted location stained with hematoxylin and eosin；（D） SEM pictures of embedded catheters after different treatments， the embedded catheters were shown in the inset photos， scale bar， 2 μm

References 35

[1]	ANTIMICROBIAL RESISTANCE C. Global burden of bacterial antimicrobial resistance in 2019： a systematic analysis［J］. Lancet， 2022， 399（10325）： 629-655.
[2]	POOLE K. Pseudomonas aeruginosa： resistance to the max［J］. Front Microbiol， 2011， 2： 65.
[3]	SMITH W P J， WUCHER B R， NADELL C D， et al. Bacterial defences： mechanisms， evolution and antimicrobial resistance［J］. Nat Rev Microbiol， 2023， 21（8）： 519-534.
[4]	KARYGIANNI L， REN Z， KOO H， et al. Biofilm matrixome： extracellular components in structured microbial communities［J］. Trends Microbiol， 2020， 28（8）： 668-681.
[5]	PRANANTYO D， YEO C K， WU Y， et al. Hydrogel dressings with intrinsic antibiofilm and antioxidative dual functionalities accelerate infected diabetic wound healing［J］. Nat Commun， 2024， 15（1）： 954.
[6]	GENG W C， SESSLER J L， GUO D S. Supramolecular prodrugs based on host-guest interactions［J］. Chem Soc Rev， 2020， 49（8）： 2303-2315.
[7]	BIRD R E， LEMMEL S A， YU X， et al. Bioorthogonal chemistry and its applications［J］. Bioconjug Chem， 2021， 32（12）： 2457-2479.
[8]	HANG H C， YU C， KATO D L， et al. A metabolic labeling approach toward proteomic analysis of mucin-type O-linked glycosylation［J］. Proc Natl Acad Sci USA， 2003， 100（25）： 14846-14851.
[9]	LIU C， NIU J， CUI T， et al. A motor-based carbonaceous nanocalabash catalyst for deep-layered bioorthogonal chemistry［J］. J Am Chem Soc， 2022， 144（42）： 19611-19618.
[10]	TORNØE C W， CASPAR C， MELDAL M. Peptidotriazoles on solid phase：［1，2，3］-triazoles by regiospecific copper（Ⅰ）- catalyzed 1，3-dipolar cycloadditions of terminal alkynes to azides［J］. J Org Chem， 2002， 67： 3057-3064.
[11]	WANG F， ZHANG Y， LIU Z， et al. A biocompatible heterogeneous MOF-Cu catalyst for in vivo drug synthesis in targeted subcellular organelles［J］. Angew Chem Int Ed， 2019， 58（21）： 6987-6992.
[12]	WANG Z， NIU J， ZHAO C， et al. A bimetallic metal-organic framework encapsulated with DNAzyme for intracellular drug synthesis and self-sufficient gene therapy［J］. Angew Chem Int Ed， 2021， 60（22）： 12431-12437.
[13]	ZHAO H， ZHAO C， LIU Z， et al. A polyoxometalate-based pathologically activated assay for efficient bioorthogonal catalytic selective therapy［J］. Angew Chem Int Ed， 2023， 62（32）： e202303989.
[14]	ZHU J， YOU Y， ZHANG W， et al. Boosting endogenous copper（Ⅰ） for biologically safe and efficient bioorthogonal catalysis via self-adaptive metal-organic frameworks［J］. J Am Chem Soc， 2023， 145（3）： 1955-1963.
[15]	YOU Y， LIU H， ZHU J， et al. A DNAzyme-augmented bioorthogonal catalysis system for synergistic cancer therapy［J］. Chem Sci， 2022， 13（26）： 7829-7836.
[16]	YOU Y， DENG Q， WANG Y， et al. DNA-based platform for efficient and precisely targeted bioorthogonal catalysis in living systems［J］. Nat Commun， 2022， 13（1）： 1459.
[17]	YIN W Y， YU J， LV F T， et al. Functionalized nano-MoS with peroxidase catalytic and near-infrared photothermal activities for safe and synergetic wound antibacterial applications［J］. ACS Nano， 2016， 10（12）： 11000-11011.
[18]	JIANG P， ZHANG L， LIU X， et al. Tuning oxidant and antioxidant activities of ceria by anchoring copper single-site for antibacterial application［J］. Nat Commun， 2024， 15（1）： 1010.
[19]	ZHANG D， LI M， CHEN S， et al. Novel palladium hydride surface enabling simultaneous bacterial killing and osteogenic formation through proton capturing and activation of antioxidant system in immune microenvironments［J］. Adv Mater， 2024， 36（31）： e2404485.
[20]	LIN R B， HE Y， LI P， et al. Multifunctional porous hydrogen-bonded organic framework materials［J］. Chem Soc Rev， 2019， 48（5）： 1362-1389.
[21]	WANG B， LIN R B， ZHANG Z， et al. Hydrogen-bonded organic frameworks as a tunable platform for functional materials［J］. J Am Chem Soc， 2020， 142（34）： 14399-14416.
[22]	CHEN G， HUANG S， MA X， et al. Encapsulating and stabilizing enzymes using hydrogen-bonded organic frameworks［J］. Nat Protoc， 2023， 18（7）： 2032-2050.
[23]	LIU S， SUN Y. Co-encapsulating cofactor and enzymes in hydrogen-bonded organic frameworks for multienzyme cascade reactions with cofactor recycling［J］. Angew Chem Int Ed， 2023， 62（42）： e202308562.
[24]	TANG Z， LI X， TONG L， et al. A biocatalytic cascade in an ultrastable mesoporous hydrogen-bonded organic framework for point-of-care biosensing［J］. Angew Chem Int Ed， 2021， 60（44）： 23608-23613.
[25]	YU D， ZHANG H， LIU Z， et al. Hydrogen-bonded organic framework （HOF）-based single-neural stem cell encapsulation and transplantation to remodel impaired neural networks［J］. Angew Chem Int Ed， 2022， 61（28）： e202201485.
[26]	YIN Q， ZHAO P， SA R J， et al. An Ultra-robust and crystalline redeemable hydrogen-bonded organic framework for synergistic chemo-photodynamic therapy J］. Angew Chem Int Ed， 2018， 57（26）： 7691-7696.
[27]	YA J， ZHANG H， QIN G， et al. A biocompatible hydrogen-bonded organic framework （HOF） as sonosensitizer and artificial enzyme for in-depth treatment of Alzheimer's disease［J］. Adv Healthc Mater， 2024， 13（29）： e2402342.
[28]	ZHANG H， YU D， LIU S， et al. NIR-Ⅱ hydrogen-bonded organic frameworks （HOFs） used for target-specific amyloid-β photooxygenation in an Alzheimer's disease model［J］. Angew Chem Int Ed， 2021， 61（2）： e202109068.
[29]	ZOU Y， LIU H X， CAI L， et al. Strategy to efficient photodynamic therapy for antibacterium： donor-acceptor structure in hydrogen-bonded organic framework［J］. Adv Mater， 2024， 36（35）： e2406026.
[30]	LIU B T， PAN X H， NIE D Y， et al. Ionic hydrogen-bonded organic frameworks for ion-responsive antimicrobial membranes［J］. Adv Mater， 2020， 32（48）： 2005912.
[31]	HUANG C， ZHAO C， SUN Y， et al. A hydrogen-bonded organic framework-based mitochondrion-targeting bioorthogonal platform for the modulation of mitochondrial epigenetics［J］. Nano Lett， 2024， 24（29）： 8929-8939.
[32]	HUANG C， ZHAO C， DENG Q， et al. Hydrogen-bonded organic framework-based bioorthogonal catalysis prevents drug metabolic inactivation［J］. Nat Catal， 2023， 6（8）： 729-739.
[33]	MAKVANDI P， SONG H， YIU C K Y， et al. Bioengineered materials with selective antimicrobial toxicity in biomedicine［J］. Mil Med Res， 2023， 10（1）： 8.
[34]	NIU J， WANG L， CUI T， et al. Antibody mimics as bio-orthogonal catalysts for highly selective bacterial recognition and antimicrobial therapy［J］. ACS Nano， 2021， 15（10）： 15841-15849.
[35]	LV J， LI B， LUO T， et al. Selective photothermal therapy based on lipopolysaccharide aptamer functionalized MoS₂ nanosheet-coated gold nanorods for multidrug-resistant pseudomonas aeruginosa infection［J］. Adv Healthc Mater， 2023， 12（15）： 2202794.

Synthesis of Hydrogen-Bonded Organic Framework Nanoenzyme for Targeting Antibacterial Applications

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