Enzymes are a category of biocatalysts that management many catalytic processes akin to metabolism, vitamin, and vitality conversion in organisms, and most reactions intently associated to life processes are enzyme-catalyzed reactions [1]. In most cancers remedy, enzymes can be utilized as therapeutic targets, instruments, and biocatalytic medication [2], [3], [4]. For instance, proteolysis-targeting chimera (PROTAC) protein degraders, which have turn into very talked-about in recent times, use their particular molecular construction to bind goal proteins to E3 ligase to degrade them [5], [6]. Glucose oxidase (GOx) successfully depleted glucose in most cancers cells, offering an method to hunger remedy [7], [8]. Nonetheless, biocatalytic medication based mostly on pure enzymes have been restricted of their additional analysis and software by inherent defects akin to poor stability, susceptibility to degradation, immunogenicity, and lack of focusing on [4], [9]. Because of this, for the reason that first report of horseradish peroxidase (HRP)-like exercise of Fe3O4 nanoparticles (NPs) by Yan et al. [10], researchers have targeted on discovering and creating novel enzyme mimics or nanozymes, and several other anticancer nanomedicines have been developed based mostly on them [11], [12], [13]. For instance, nanozymes with peroxidase (POD)-like exercise can convert H2O2 that’s overexpressed within the tumor microenvironment (TME) into reactive oxygen species (ROS) akin to hydroxyl radicals (•OH), which have a robust oxidative capability and may kill most cancers cells [14], [15]. Catalase (CAT) mimetics, then again, can cut back H2O2 to O2 to alleviate tumor hypoxia, thereby enhancing the efficacy of many oxygen-dependent therapies [16], [17]. Typically, nanozymes are multi-enzyme in nature and will also be mixed with different pure enzymes or enzyme mimics to type cascade enzyme techniques, or together with different therapies to extra successfully counteract the hostile results of a selected TME on the remedy and improve therapeutic efficacy [18], [19].
Two-dimensional (2D) transition steel carbides, nitrides, and carbonitrides (MXenes) are amongst at the moment’s hottest supplies and have been chosen by the Worldwide Union of Pure and Utilized Chemistry (IUPAC) as one of many IUPAC’s 2024 Prime Ten Rising Applied sciences in Chemistry [20]. MXenes have distinctive physicochemical properties together with a big particular floor space, flexibility, engaging ceramic properties, and electrical conductivity [21], [22], which make them extensively researched within the fields of vitality storage [23], [24], environmental safety [25], [26], catalysis [27], [28], sensing [29], [30], and electromagnetic shielding and absorption [31], [32]. As well as, current years have seen a rise in analysis efforts exploring the potential of MXene within the area of biomedical purposes [33], [34], [35]. Like many different 2D supplies, akin to graphene, black phosphorus, and 2D transition steel sulfides, MXene has photothermal properties [36], [37]. Due to this fact, to our data, the primary time MXene was utilized in most cancers remedy was in 2017 when Shi’s group used Ti3C2Tx nanosheets for photothermal remedy (PTT) [38], [39]. This is likely one of the most essential purposes of MXene in illness remedy [38], [39], [40], [41]. Curiously, transition steel parts akin to Ti, V, and Nb are sometimes present in decrease valence states in MXenes. For instance, within the first MXene ready, Ti3C2Tx, Ti is current in + 2 and + 3 valences as a substitute of + 4 [42], [43]. Thus, MXenes are usually reductive. Mixed with their 2D constructions, the frequent MXenes represented by Ti3C2Tx have good free-radical and ROS scavenging talents [44], [45], [46]. Ti3C2Tx, particularly, can decompose H2O2 into H2O and O2, exhibiting CAT-like conduct [42], [43]. Due to this fact, we proposed the speculation that Ti3C2Tx MXene is a CAT mimetic and constructed Ti3C2Tx nanosheets as the premise for a cascade enzyme system Ti3C2Tx-GOx/DOX-PEG, which is loaded with each GOx and the anticancer drug doxorubicin (DOX) [42], [43]. The CAT-like properties of Ti3C2Tx allow it to decompose the overexpressed H2O2 in TME to provide O2 and alleviate hypoxia, thereby sensitizing DOX for chemotherapy. As well as, O2 will also be provided to GOx to be used in hunger remedy. One of many degradation merchandise of glucose, H2O2, can in flip be provided to Ti3C2Tx. Mixture remedy introduces a gentle PTT of Ti3C2Tx at low doses. Yang’s group additionally reported a thermoelectric heterojunction named Pt-TiO2-x/Ti3C2Tx-PEG based mostly on Ti3C2Tx, which makes use of its CAT-like property to provide O2 to most cancers cells, for the era of 1O2 and •O2– by ultrasound and photo-thermoelectric catalysis, which mix with PTT to kill most cancers cells [47]. Zhang et al. exactly anchored self-assembled S-Cu(I)-S websites to Ti3C2Tx to assemble a nanomodulator that may set off a number of tumor mixture therapies by way of a photothermal-enhanced cascade modulation pathway [48].
Nonetheless, though Ti3C2Tx MXene has CAT-like properties that may alleviate hypoxia within the TME to a sure extent, its enzymatic exercise is weak, and its capacity to transform hypoxic TME is proscribed [42], [43]. Conversely, GOx, as a pure enzyme, has inherent defects akin to poor stability and susceptibility to inactivation, which make it topic to many limitations when taking part within the building of anticancer cascade enzyme techniques [4], [9]. As one of many first nanomaterials to be systematically investigated, gold nanoparticles (Au NPs) or colloidal gold have additionally been proven to own multi-enzymatic actions, together with GOx- and POD-like actions [49], [50]. As one of many valuable metals, gold is extensively utilized in biodetection and anticancer fields as a result of its glorious electrochemical properties and low biotoxicity [51], [52]. Due to this fact, changing GOx with Au NPs to assemble CAT/GOx-like anticancer cascade enzyme techniques together with Ti3C2Tx is a doable method that may overcome the inherent defects of GOx. And compounding totally different conductors or semiconductors with very totally different constructions and catalytic actions is likely one of the methods to alter the catalytic capacity of a fabric [53], [54], [55]. Due to this fact, we additionally count on that compounding Au NPs with Ti3C2Tx will result in extra attention-grabbing nanozymes.
Because of the lowering nature of Ti3C2Tx, Zhang et al. just lately reported an in situ discount technique for depositing numerous metals akin to Au, Pd, Ag, and Pt on Ti3C2Tx [56]. We’ve got independently found this technique and used it to arrange Au NPs-loaded Ti3C2Tx (Ti3C2Tx-Au) on this work. The complexation of Au NPs with Ti3C2Tx imparts GOx- and POD-like properties to Ti3C2Tx-Au. This permits the development of a CAT/GOx/POD-like cascade enzyme system. Introducing Au NPs dramatically enhances the CAT-like exercise of Ti3C2Tx. This might successfully alleviate the hostile results of hypoxia on the remedy. We current a doable means of Ti3C2Tx-Au-catalyzed H2O2 decomposition for oxygen manufacturing and a doable mechanism for its enhanced CAT-like exercise by Density practical idea (DFT) calculations, i.e., Au NPs act as a bridge for electron switch in the course of the response. As proven in Scheme 1, we additional modified Ti3C2Tx-Au with polyethylene glycol (PEG) to acquire Ti3C2Tx-Au-PEG (TANP), which is extra appropriate for in vivo purposes. As soon as TANP accumulates within the tumor and enters the most cancers cell via the Enhanced Permeability and Retention impact, it could actually catalyze enhanced enzymatic cascade reactions contained in the cell. The reactions maintain glucose consumption and oxygen manufacturing to alleviate hypoxia, and ROS manufacturing, which will also be enhanced by the photothermal impact. Because of this, TANP permits extremely efficient mixed photothermal/biocatalytic remedy. This work is predicted to offer new concepts for creating novel multifunctional nanozymes with anticancer exercise.
