Single-atom engineering of metal-organic frameworks toward healthcare

Enzymes participate in efficient biochemical reactions and maintain normal life activities living systems. Enzyme-based therapeutic interventions have been a major area of focus development the pharmaceutical industry. Taking advantage advanced nanotechnology smart design nanosystems for mimicking enzymatic behavior natural enzymes, nanozymes with tunable shown their promising application potential assisting or even substituting conventional pharmaceuticals. Remarkably, single-atomic 100% metal-atom utilization efficiency, satisfying catalytic performance, minimized systematic cytotoxicity present great promise toward practical applications. In this review, we highlight recent research advances metal-organic-framework-based healthcare applications portray principles underlying mechanisms, thus suggesting directions future rapidly developing field. Single-atomic nanocatalysts/nanozymes (SACs/SAEs) emerged as frontier on account maximum atom-utilization efficiency well-defined localized structure. Metal-organic frameworks (MOFs) featuring structural diversity functional tunability are host materials constructing SACs/SAEs. Further, pyrolysis MOF precursors under certain conditions can lead to formations MOF-derived first introduce classification mechanisms nanozymes, comprehensive characterization techniques SACs/SAEs, various synthetic methodologies MOF-based Next, SACs/SAEs area, i.e., cancer treatment, biosensing, antibacterial approaches, reactive oxygen species scavenging, environmental protection. Finally, summarize insights gain from these studies discuss possible challenges deeper understanding emerging field, offering opportunities leap over into new era next-generation biosafe IntroductionAll phenomena nature associated including many proteases non-metal metal catalytically active centers (cofactor), which systems earth.1Benkovic S.J. Hammes-Schiffer S. A perspective enzyme catalysis.Science. 2003; 301: 1196-1202Crossref PubMed Scopus (895) Google Scholar For instance, cytochrome P450 is large superfamily enzymes containing heme cofactor, acts monooxygenase. The site four-nitrogen-coordinated, isolated Fe element. typical reaction process insert an atom organic substrates, another reduced water.2Gonzalez F.J. Gelboin H.V. Human cytochromes P450: evolution cDNA-directed expression.Environ. Health Perspect. 1992; 98: 81-85Crossref Scholar,3Fasan R. Tuning oxidation catalysts.ACS Catal. 2012; 2: 647-666Crossref (240) Along Fe3O4 nanoparticles exhibiting excellent peroxidase (POD) activity, concept was formally proposed 2007.4Gao L. Zhuang J. Nie Zhang Y. Gu N. Wang T. Feng Yang D. Perrett Yan X. Intrinsic peroxidase-like activity ferromagnetic nanoparticles.Nat. Nanotechnol. 2007; 577-583Crossref (3109) As generation artificial they perfectly integrate advantages both nanomaterials such low production costs, properties, high stability. Further revealed that POD mechanism nanozyme similar horseradish (HRP), behaving “ping-pong mechanism,” where catalyzes hydrogen peroxide produce hydroxyl radicals generate Fe3O4-radical complex, latter then 3,3?,5,5?-tetramethylbenzidine (TMB) color changes. Recently, therapy based used strategy combat substrate selectivity. Subsequently, different successfully constructed tumor-specific purposes trigger levels specific chemical markers within tumor microenvironment sensitizing cells following treatments. example, specifically overexpressed free radicals, causing irreversible damage key components (lipids, proteins, DNA) cells.5Huo M. Chen Shi Tumor-selective nanomedicine by nanocatalyst delivery.Nat. Commun. 2017; 8: 357Crossref (563) ScholarAlthough exhibit comparable higher stability most reported oxides (e.g., Fe3O4, Mn3O4, CuO, CeO2) precious metals Au, Ag, Pd, Pt). Similar heterogeneous catalysts, significant promises broad range reactions. However, sites often located at corner, edge, facet crystals, making them difficult normalize properties. On other hand, degrade metabolize when vivo. Possible leakage ions also causes unpredictable cytotoxicity, resulting biocompatibility biosafety issues. highly ordered multilevel structures endow selectivity, understandable operating mechanisms. related factors, size, morphology, surface properties nanoparticles. Therefore, it establish corresponding theories types nanozymes. To maximize behavior, one reduce size boosting selectivity.Catalysis plays essential role all kinds biological transformations.6Baleizão C. Garcia H. Chiral salen complexes: overview recoverable reusable homogeneous catalysts.Chem. Rev. 2006; 106: 3987-4043Crossref (594) Scholar,7Xia Q.H. Ge H.Q. Ye C.P. Liu Z.M. Su K.X. Advances asymmetric epoxidation.Chem. 2005; 105: 1603-1662Crossref (0) extremely important transformations occur nanocatalysts. With decreasing, portion low-coordinated atoms act would increase dramatically. way, enhanced be achieved since mass usually number exposed increases ten times nanoparticle decreases 30 3 nm (Figure 1). addition, change may alter atomic conformation, electronic structures, defects catalysts. When downsizing supporting matrix scale, termed nanocatalysts (SACs). SACs atomically dispersed regarded catalysis.8Zhao Z. Cao Peng Q. Li Atomic electrocatalysts water splitting, reduction selective oxidation.Chem. Soc. 2020; 49: 2215-2264Crossref Scholar, 9Beniya A. Higashi Towards dense single-atom catalysts automotive applications.Nat. 2019; 590-602Crossref (81) 10Babucci Guntida Gates B.C. Atomically supports zeolites metal-organic frameworks: structure, bonding, reactivity, catalysis.Chem. 120: 11956-11985Crossref (17) Moreover, behave ultrahigh reactivity selectivity diverse Obviously, offers wide spectrum deeply understand scale build bridge between catalysis.Since enzyme-based nanocatalyst-based reactions, tremendous efforts devoted novel (SAEs) activities.11Xiang W. Single-atom biomedicine.Adv. Mater. 32: 1905994Crossref (68) Scholar,12Jiao Wu Zhu Du et al.When meet catalysis.Angew. Chem. Int. Ed. 59: 2565-2576Crossref (133) Actually, possess common nature, single-Fe hemoglobin, single-Mg chlorophyll, single-Mo nitrogenase. Inspired unique electron rationally developed Generally, feasible anchor (metal atoms, ions, compounds) onto solid materials, oxides, silica, zeolite, carbon materials. Although promising, found disordered limited, inhomogeneous distribution interactions single-metal groups Consequently, continuous discovery offer more allow precise control implementation functionalities. (MOFs), nodes linkers, attracted lot attention areas during past decades.13Horcajada P. Gref Baati Allan P.K. Maurin G. Couvreur Férey Morris R.E. Serre biomedicine.Chem. 112: 1232-1268Crossref (2886) 14Wu M.X. Y.W. framework (MOF)-based drug/cargo delivery therapy.Adv. 29: 1606134Crossref (952) 15Rojas Horcajada removal contaminants water.Chem. 8378-8415Crossref (152) 16Bavykina Kolobov Khan I.S. Bau J.A. Ramirez Gascon catalysis: progress, trends, perspectives.Chem. 8468-8535Crossref 17Ni K. Luo Nash G.T. Lin Nanoscale immunotherapy.Acc. Res. 53: 1739-1748Crossref (24) 18Gao Pan Tang B. Antitumor agents frameworks.Angew. 2021; 60: 16763-16776Crossref (6) Because diversity, tunability, MOFs derivatives adjustable coordination environments, robust stability.19Wei Y.S. Zou Xu framework-based single sites.Chem. 12089-12174Crossref (154) These hold enzymes. characters provide indeed versatile platform biomedicine becoming interdisciplinary area. particular, carbon-based SAEs strong substrates sites, endowing opportunity become nanozymes.In progress focused rising anchoring biomedical Accordingly, main oxidoreductases well functionalities metabolism synthesis strategies designing structure information investigated using powerful techniques. Furthermore, elaborate healthcare-related (ROS) protection 2). At same time, relationship property presented deep process. challenge prospects revealed.Figure 2Applications nanozymesShow full captionSchematic illustration applications.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Classification oxidoreductasesThe rapid makes synthesize controlled fields.20Yang Nanocatalytic medicine.Adv. 31: 1901778Crossref (141) 21Wang Wan Recent research.Adv. 1805368Crossref (149) 22Wu Lou Qin Wei Nanomaterials enzyme-like characteristics (nanozymes): (II).Chem. 48: 1004-1076Crossref 23Xue C.C. M.H. Sutrisno B.B. Zhao Hu Cai K.Y. Yu S.H. Bioresorbable scaffolds biocatalytic chemotherapy situ modulation postoperative tissue repair.Adv. Funct. 2008732Crossref (1) pioneering work POD-mimicking Fe3O4,4Gao numerous spent mimic abundant system, POD, glutathione (GPx), oxidase (OXD), superoxide dismutase (SOD), catalase (CAT), uses.24Huang Ren Qu Nanozymes: classification, regulation, applications.Chem. 119: 4357-4412Crossref (656) 25Feng Xie Qian Zhou al.An ultrasmall SnFe2O4 endogenous depletion synergistic 2006216Crossref (18) 26Jana Bindra A.K. Guo Ultrasmall alloy ultrasound- near-infrared light-promoted ablation.ACS Nano. 15: 7774-7782Crossref (2) Typically, divided two categories according source activity: combined intrinsic activities. Compared mentioned earlier, regular arrangements ligands porous pores enable sufficient contact facilitating diffusion transmission products. Additionally, uniform channel shape size-selective allowing controllable selection molecules. Thus, section, five 3). Meanwhile, CAT, OXD, SOD, GPx presented.Figure 3Enzymatic oxidoreductasesShow captionScheme diagram catalyzed oxidoreductases: GPx.View (PPT)PeroxidasePOD consists could catalyze presence H2O2 peroxides (R–OOH). During process, reduced, typically serve donors. It known originated Fenton-like reaction. 2007, coworkers hidden activity.4Gao Interestingly, commonly involve multivalent (Fe2+/Fe3+, Mn2+/Mn3+, Cu+/Cu2+) initiate reaction.27Nath I. Chakraborty Verpoort F. Metal enzymes: analogy.Chem. 2016; 45: 4127-4170Crossref Scholar,28Li Hou Xue State-of-the-art iron-based therapy.Nanoscale Horiz. 5: 202-217Crossref By coordinating created optimized Fenton/Fenton-like should good choices adsorbed subsequent breaking down peroxy bond radical (•OH). Fe-MIL-88 (MIL = Materials Institute Lavoisier) sensor detect dopamine through fluorescence. possesses •OH H2O2. Fe3+ ion Fe2+ accelerate Fenton fluorescence.29Zhao Jiang Mu turn-on fluorescence frameworks-hydrogen peroxide-o-phenylenediamine system.Talanta. 159: 365-370Crossref (48) Ranji-Burachaloo partial MIL-88B (Fe)–NH2 hydrothermal method. catalysis, pH-triggered release induce catalysis.30Ranji-Burachaloo Karimi Fu Gurr P.A. Dunstan D.E. Qiao G.G. MOF-mediated destruction cell's own peroxide.ACS Appl. Interfaces. 9: 33599-33608Crossref (87) Notably, accompanied partially explaining further ultrathin nanosheets exhibited performance bulk analogs due sites.31Cheng Ding Muhammad al.Monitoring heparin live rats mimics.Anal. 89: 11552-11559Crossref (131) enhance Fe–N–C Fe-Nx moiety supported via high-temperature Fe–Zn-MOF.32Niu Tian al.Unprecedented peroxidase-mimicking moieties hosted derived carbon.Biosens. Bioelectron. 142: 111495Crossref (59) Due 57.76 U mg?1, value POD. system showed biosensing detection (0.1?10 L?1) limit 0.054 L?1.Glutathione peroxidaseAnother oxidation-reduction GPx. function protect organism against oxidative stress damage.33Bhabak K.P. Mugesh Functional mimics peroxidase: bioinspired antioxidants.Acc. 2010; 43: 1408-1419Crossref (370) depends Se-cysteine center reduces intracellular assistance (GSH) formation oxidized (GSSG). vital maintaining redox balance, still suffers some issues poor bioavailability. Nanozymes well-known GPx-mimicking MnO2 nanoparticles, GSH GSSG Mn4+ Mn2+ time.34Singh Savanur M.A. Srivastava D’Silva modulatory Mn3O4 multi-enzyme provides cytoprotection human Parkinson’s disease model.Angew. 56: 14267-14271Crossref Except MnO2, V2O5, CeO2, nanoscale V2O5 nanowires convert H2O GSH, protecting stress.35Vernekar A.A. Sinha Paramasivam P.U. D'Silva An antioxidant uncovers cytoprotective vanadia nanowires.Nat. 2014; 5301Crossref (182) Very recently, applied engineered ligand tailor series MIL-47(V)-X H 1,4-benzenedicarboxylicacid F, Br, NH2, CH3, OH groups.36Wu Cheng al.Ligand-dependent engineering MIL-47(V) therapy.Angew. 1227-1234Crossref (11) as-prepared named MIL-47(V)-F, MIL-47(V)-Br, MIL-47(V)-NH2, MIL-47(V)-CH3. Results that, among isostructural MOFs, MIL-47(V)-NH2 possessed highest anti-inflammation vitro vivo.OxidaseOXD big subclass molecular O2 acceptor substrates. noted serving H2O, H2O2, (•O2?) accepting four, two, electron, respectively Among c OXD final component transport chain mitochondrion allows utilize energy generation. Other examples glucose monoamine P450, nicotinamide adenine dinucleotide phosphate sulfhydryl oxidize thiol groups. Rossi “naked” gold acid O2.37Comotti Della Pina Matarrese particles.Angew. 2004; 5812-5815Crossref phenomenon Au adsorb hydrated anion form electron-rich species, nucleophilic attacking reagents capture dissolved molecule. Then, as-formed dioxogold intermediates (Au+-O2? Au2+-O22?) transfer electrons dioxygen glucose, finally generating gluconic integrating upconversion coated Zr/Fe-MOF core-shell nanostructure ([email protected]).38He Ni Fan al.Solvent-assisted self-assembly biocatalyst cascade driven photodynamic therapy.J. Am. 6822-6832Crossref (51) results [email protected] nanoreactor effective biocatalysis decompose singlet (1O2) near infrared (NIR) irradiation. case, fabricated MIL-53(Fe)-X (X H, OH, Cl, NO2) X group 1,4-benzenedicarboxylic ligand.39Wu Jin al.Hammett oxidase-mimicking protein-engineering-inspired strategy.Adv. 33: 2005024Crossref (8) them, MIL-53(Fe)-NO2 10-fold OXD-mimicking than unsubstituted MIL-53(Fe) strongest electron-withdrawing effect –NO2 group.Superoxide dismutaseIt generated ROS aerobic respiratory chain.40Lushchak V.I. Free its classification.Chem. Biol. Interact. 224: 164-175Crossref (646) Scholar,41Farmer K.J. Sohal R.S. Relationship aging housefly, Musca domestica.Free Radic. Med. 1989; 7: 23-29Crossref produced lipid peroxidation, speed up body’s skin internal organs, diseases, cardiovascular cancer, seriously endangering health. •O2? converted SOD disproportion