Surface-Modified Nanozymes for Enhanced and Selective Catalysis

Abstract

Surface-modified catalytic nanoparticles (nanozymes) are introduced as hybrid nanoparticles overcoming basic limitations associated with bare nanozymes that include moderate catalytic turnovers, lack of substrate selectivity and chiroselectivity, and poor or nonselective permeabilities into biomembrane. This review introduces aptamer-modified nanozymes, receptor (cyclodextrins)- or ligand (amino acids, peptides)-functionalized catalytic nanoparticles, and molecularly imprinted polymer-coated nanozymes as hybrid frameworks improving the catalytic properties and selective/chiroselective functions of the nanozymes. Binding of the reaction substrates to the aptamers, ligands, or molecular-imprinted sites, by affinity interactions, concentrates the substrates in spatial proximity to the nanozyme catalytic sites ("molarity effect"), thereby enhancing the catalytic performance of the frameworks. Specific and chiroselective binding interactions of the substrates to the surface modifiers lead to selective or chiroselective chemical transformations. Moreover, by appropriate molecular engineering of the surface modifiers on the nanozymes, catalytic functions lacking in the parent bare nanozymes are demonstrated. Potential applications of surface-modified nanozymes are discussed.

Keywords: Aptamer; Chiroselectivity; Molecular-imprinted polymer; Nanomedicine; Nanoparticle; Reactive oxygen species (ROS).

1

(A) Aptamer-modified Cu²⁺-C-dots aptananozyme for the catalyzed H₂O₂ oxidation of dopamine to aminochrome or the chiroselective oxidation of l-/d-DOPA to aminochrome. (B) Panel I: a set of configurations of dopamine aptamer-functionalized Cu²⁺-C-dots aptananozymes. Panel II: rates of dopamine oxidation by H₂O₂ in the presence of the set of aptananozymes shown in Panel I, as a function of dopamine concentrations. Panel III: rates of chiroselective oxidation of l-/d-DOPA with H₂O₂ by aptananozyme-i as compared to the separated Cu²⁺-C-dots and dopamine aptamer in the presence of various concentrations of l-/d-DOPA ((a) oxidation of l-DOPA by the aptananozyme-i; (b) oxidation of d-DOPA by the aptananozyme-i; (c, d) oxidation of l-DOPA (c) or d-DOPA (d) by the separated Cu²⁺-C-dots and dopamine aptamer). Reproduced from ref . Available under a CC-BY 4.0 license. Copyright 2021 ACS. (C) Panel I: electron spin resonance spectrum of the hydroxyl radical (^•OH) generated by the dopamine aptamer-modified Ce⁴⁺-C-dots in the presence of H₂O₂. Panel II: mechanistic pathway corresponding to the dopamine aptamer-modified Ce⁴⁺-C-dots aptananozyme catalyzing the H₂O₂ oxidation of dopamine to aminochrome. Reproduced from ref . Available under a CC-BY 4.0 license. Copyright 2022 ACS.

2

(A) Schematic ROS-driven apoptosis of cancer cells using the AS1411 aptamer or MUC-1 aptamer-modified Ce⁴⁺-C-dots as ROS generating agent. (B) Panel I: cell viability of MDA-MB-231 breast cancer cells and MCF-10A epithelial breast cells ((a) nontreated control cells; (b) treated with AS1411 aptamer-modified Ce⁴⁺-C-dots; (c) treated with MUC-1 aptamer-modified Ce⁴⁺-C-dots). Panel II: temporal MDA-MB-231 tumor growth treated with (a) Ce⁴⁺-C-dots, (b) AS1411 aptamer-modified Ce⁴⁺-C-dots, (c) MUC-1 aptamer-modified Ce⁴⁺-C-dots, and (d) control PBS buffer. Reproduced from ref . Available under a CC-BY 4.0 license. Copyright 2022 ACS. (C) Schematic ROS-driven apoptosis of cancer cells using Au NPs stabilized with polyadenine/AS1411 aptamer strand as bioreactor generating ROS agent. (D) Panel I: cell viability of MDA-MB-231 breast cancer cells and MCF-10A epithelial breast cells ((a) nontreated control cells; (b) treated with AS1411 aptamer-expanded polyadenine-stabilized Au NPs). Panel II: temporal MDA-MB-231 tumor growth treated with (a) random sequence-expanded polyadenine-stabilized Au NPs, (b) polyadenine-stabilized Au NPs, and (c) AS1411 aptamer-extended polyadenine-stabilized Au NPs. Reproduced from ref . Available under a CC-BY 4.0 license. Copyright 2022 ACS.

3

(A) Schematic single strand (1) or duplex nucleic acid (1)/(2)-modified Au NPs for the chiroselective aerobic oxidation of l-/d-glucose to gluconic acid and H₂O₂, probed by analyzing the resulting H₂O₂ by the secondary HRP-catalyzed oxidation of ABTS^2– to the colored ABTS^–•. (B) Chiroselective aerobic oxidation of l-/d-glucose catalyzed by the (1)-modified Au NPs (Panel I) and (1)/(2)-modified Au NPs (Panel II). Panel III: chiroselective aerobic oxidation of l-/d-glucose by the (1)- or (1)/(2)-modified Au NPs as a function of the concentration of the nucleic acid modifiers used to coat Au NPs. Reproduced from ref . Copyright 2015 ACS.

4

(A) β-CD-modified Cu²⁺-C-dots as a receptor-modified nanozyme for enhanced oxidation of dopamine by H₂O₂. (B) Rates of dopamine oxidation by H₂O₂ at different concentrations of dopamine: (i) in the presence of the integrated β-CD/Cu²⁺-C-dots nanozyme; (ii) in the presence of nonmodified Cu²⁺-C-dots. Reproduced from ref . Copyright 2017 ACS. (C) Synthesis of β-CD-modified Pd@Au NPs for the enhanced oxidation of TMB. (D) Time-dependent absorbance changes upon oxidation of TMB to TMB^+• by H₂O₂: (i) in the presence of β-CD-modified Pd@Au NPs; (ii) in the presence of bare Pd@Au NPs. (E) Application of the β-CD-modified Pd@Au NPs for the colorimetric detection of glucose. (F) Calibration curve relating the absorbance changes of the colorimetric probe (TMB^+•) to variable concentrations of glucose, sensed by the β-CD-modified Pd@Au NPs. Reproduced with permission from ref . Copyright 2020 Springer Nature. (G) Protamine-functionalized Rh/rGO acting as a hybrid nanozyme for the aerobic oxidation of uric acid to allantoin. (H) Panel I: time-dependent absorbance changes upon aerobic oxidation of uric acid by (i) the protamine-functionalized Rh/rGO and (ii) the bare Rh/rGO. Panel II: optical micrograph corresponding to (a) the nontreated urate crystal and (b) the urate crystal treated with protamine-functionalized Rh/rGO. Reproduced from ref . Copyright 2024 ACS.

5

(A) l-/d-cysteine-modified Au NPs encapsulated in SiO₂ for the chiroselective oxidation of l-/d-DOPA to dopachrome by H₂O₂. (B) Absorbance corresponding to the catalyzed H₂O₂ oxidation of l-/d-DOPA to dopachrome by using l-cysteine-modified Au NPs/SiO₂ (blue), d-cysteine-modified Au NPs/SiO₂ (red), and bare Au NPs/SiO₂ (gray). Reproduced with permission from ref . Copyright 2018 Wiley. (C) Schematic chiroselective aerobic oxidation of l-/d-DOPA by l-or d-phenylalanine-modified CeO₂ particles to dopachrome. (D) Panel I: rates of l-DOPA (i) and d-DOPA (ii) oxidation catalyzed by the d-phenylalanine-modified CeO₂. Panel II: rates of d-DOPA (i) and l-DOPA (ii) oxidation catalyzed by the l-phenylalanine-modified CeO₂. Reproduced with permission from ref . Copyright 2017 Wiley.

6

(A) Synthesis of SiO₂ thin film-assisted l-/d-tryptophan-functionalized polyacrylamide-coated Fe₃O₄ NPs as catalyst for the chiroselective coupling of l-/d-tyrosinol. (B) Panel I: schematic chiroselective H₂O₂-driven coupling of l-/d-tyrosinol by the chiral l-/d-tryptophan-modified nanoparticles shown in (A). Panel II: rates of l-/d-tyrosinol coupling catalyzed by the d-tryptophan-modified particles (blue), the L-tryptophan-modified particles (red), and the nonmodified particles (gray) in the presence of H₂O₂. Reproduced with permission from ref . Available under a CC-BY 4.0 license. Copyright 2020 RSC. (C) Schematic chiroselective hydrolysis of (+)/(−)-2-hydroxypropyl p-nitro-m-trifluoromethylphenyl phosphate using Zn²⁺-coordinated (+)/(−)-1-(2-(8-(mercapto)­octanamido)-3-(methylamino)-3-oxopropyl)-1,4,7-triazacyclononane-modified Au NPs as catalysts. (D) Hydrolysis efficacy of Zn²⁺-coordinated (+)/(−)-1-(2-(8-(mercapto)­octanamido)-3-(methylamino)-3-oxopropyl)-1,4,7-triazacyclononane-modified Au NPs toward (+)/(−)-2-hydroxypropyl p-nitro-m-trifluoromethylphenyl phosphate. Reproduced with permission from ref . Copyright 2016 Wiley.

7

(A) Schematic synthesis of Fe₃O₄ particles coated with a TMB or ABTS^2–-imprinted polyacrylamide/poly­(N-isopropylacrylamide) coating for the enhanced and selective oxidation of TMB or ABTS^2– by H₂O₂. (B) Panel I: rates of TMB oxidation by H₂O₂ yielding TMB^+• using (i) TMB-imprinted polymer-coated Fe₃O₄, (ii) bare Fe₃O₄ particles, (iii) nonimprinted polymer-coated Fe₃O₄, and (iv) ABTS^2–-imprinted polymer-coated Fe₃O₄. Panel II: rates of ABTS^2– oxidation by H₂O₂ yielding ABTS^–• using (i) ABTS^2–-imprinted polymer-coated Fe₃O₄, (ii) bare Fe₃O₄ particles, (iii) nonimprinted polymer-coated Fe₃O₄, and (iv) TMB-imprinted polymer-coated Fe₃O₄. Reproduced from ref . Copyright 2017 ACS.

8

(A) Panel I: schematic synthesis of Co²⁺-ZIF-67 NPs. Panel II: Co²⁺-ZIF-67-catalyzed oxidation of aniline to polyaniline (PAn) by H₂O₂ yielding PAn-coated Co²⁺-ZIF-67. Panel III: SEM images corresponding to bare Co²⁺-ZIF-67 particles (upper image) and PAn-coated Co²⁺-ZIF-67 particles (lower image). Panel IV: element mapping of the PAn-coated Co²⁺-ZIF-67 NPs. (B) Schematic imprinting of l-/d-DOPA sites into PAn-coated Co²⁺-ZIF-67 NPs for the chiroselective and enhanced H₂O₂ oxidation of l-/d-DOPA. (C) Panel I: temporal absorbance changes corresponding to (i) oxidation of l-DOPA in the presence of l-DOPA-imprinted NPs and H₂O₂, (ii) oxidation of d-DOPA in the presence of l-DOPA-imprinted NPs and H₂O₂, and (iii) oxidation of l-DOPA in the presence of nonimprinted PAn-coated NPs and H₂O₂. Panel II: temporal absorbance changes corresponding to (i) oxidation of d-DOPA in the presence d-DOPA-imprinted NPs and H₂O₂; (ii) oxidation of l-DOPA in the presence d-DOPA-imprinted NPs and H₂O₂; (iii) oxidation of d-DOPA in the presence nonimprinted PAn-coated NPs and H₂O₂. Reproduced from ref . Available under a CC-BY 4.0 license. Copyright 2023 Wiley.

9

(A) Panel I: schematic synthesis of Cu-ZIF NPs for the catalyzed H₂O₂ oxidation of uric acid (UA) to allantoin. Panel II: Cu-ZIF-catalyzed oxidation of aniline to polyaniline (PAn) by H₂O₂ yielding PAn-coated Cu-ZIF NPs. (B) Panel I: schematic imprinting of UA sites in PAn-coated Cu-ZIF nanoparticles. Panel II: temporal concentration changes of UA upon the H₂O₂-driven oxidation of UA to allantoin in the presence of (i) bare Cu-ZIF particles, (ii) nonimprinted PAn-coated Cu-ZIF particles, and (iii) UA-imprinted PAn-coated Cu-ZIF particles. (C) Panel I: schematic aerobic oxidation of UA to allantoin by the UA-imprinted Cu-ZIF particles. Panel II: temporal concentration changes of UA upon aerobic oxidation to allantoin in the presence of (i) UA-imprinted Cu-ZIF particles, (ii) bare Cu-ZIF particles, and (iii) nonimprinted PAn-coated Cu-ZIF particles. Panel III: kinetic analysis of the aerobic oxidation of UA by UA-imprinted PAn-coated Cu-ZIF polynanozyme. (D) Suggested mechanism for the aerobic oxidation of UA to allantoin in the presence of the UA-imprinted PAn-coated Cu-ZIF polynanozyme. Reproduced from ref . Available under a CC-BY 4.0 license. Copyright 2025 ACS.

10

(A) Panel I: schematic synthesis of benzeneboronic acid-functionalized octadecyl (C18)-polyethylene glycol (CPB). Panel II: schematic synthesis of CPB-modified graphene-encapsulated PtCo nanocrystals (PtCo@G@CPB) and antibacterial mechanism of PtCo@G@CPB against . Panel III: survival of treated with PtCo@G@CPB. Reproduced from ref . Available under a CC-BY 4.0 license. Copyright 2025 Springer Nature. (B) Panel I: schematic illustration of the self-assembly and the enzyme-like activities of the CeTA-K₁tkP nanozyme. Panel II: production of inflammatory cytokines, IL-6 (i), TNF-α (ii), and IL-1β (iii), in bronchoalveolar lavage fluid of Flu A virus (H1N1)-mediated pneumonia model in mice after treatment by CeTA-K₁tkP nanozyme as compared to the no treatment system. Reproduced with permission from ref . Copyright 2025 Spring Nature.