Single-atom nanozymes (SAzymes) have been promising candidates for tumor catalytic remedy [1], [2], [3], [4]. In view of distinct traits, like clearly outlined and exactly positioned metallic facilities, uniform coordination setting, customizable construction and composition, in addition to adaptable performance [5], [6], SAzymes are endowed with superior catalytic actions of peroxidase (POD) [7], catalase (CAT) [8], or oxidase (OXD) [9], realizing plentiful technology of reactive oxygen species (ROS) for most cancers catalytic remedy [7]. Nonetheless, SAzymes containing a sole energetic middle are unable to attain optimum adsorption states for a number of intermediates in POD or CAT-mediated catalytic reactions, resulting in decreased selectivity of ROS and in the end proscribing catalytic effectivity [10]. Moreover, the intrinsic catalytic actions of SAzymes are difficult to boost additional because of the typical configuration of a solitary central metallic atom surrounded by non-metallic atoms like carbon (C) and nitrogen (N) [4], [8], [11]. Consequently, exploring strategies to boost the catalytic actions of SAzymes and elucidate their catalytic mechanisms has emerged as a outstanding focus within the realm of SAzymes analysis.
On condition that SAzymes sometimes show an end-on adsorption configuration with H2O2, resulting in a substantial power barrier for O-O bond cleavage, which hinders the technology of energetic intermediates. Drawing inspiration from pure enzymes that includes dinuclear metallic websites (like polyphenol oxidases with a Cu-Cu binuclear energetic middle [12], cytochrome c oxidases containing a Fe-Cu hetero-binuclear energetic middle [13], [14], and methane monooxygenase with a Fe-Fe binuclear energetic middle [15]), which may improve O-O cleavage due to their distinct digital and geometric constructions [16]. Latest analysis works have indicated that modifying the interaction between bimetallic atoms, which might affect the accessibility of surface-active websites or govern catalytic websites, is essentially thought to be the important thing precept in enhancing catalytic efficacy [17], [18]. Twin-atom nanozymes (DAzymes), an enhanced iteration of SAzymes, significantly heteronuclear dual-atom nanozymes, not solely protect the deserves of monoatomic catalysts but additionally supply a extra finely-tuned coordination setting [10], [19]. Moreover, DAzymes have a better potential to regulate the D-band middle by influencing digital orbits interplay, thereby enhancing the adsorption/desorption of H2O2 and O2 intermediates [16], which ends up in elevated selectivity and catalytic effectivity in most cancers catalytic remedy.
Varied varieties of DAzymes with totally different help supplies together with carbon-based supplies [1], [7], [20], [21], or metallic oxides [22], [23], [24], have been designed and synthesized, bestowing on them numerous adsorption and catalytic capability. Therefore, it’s essential to develop appropriate helps that not solely characteristic a coordination ambiance for attaching particular person atoms but additionally improve the utilization of comparatively restricted single-atom websites. Introducing heteroatoms like B, N, F, P, or S into carbon supplies has been urged as promising help choices for anchoring metallic atoms [9], [20]. In the meantime, optimizing the construction of carbon substrates, together with nanospheres [25], [26], [27], nanoblocks [28], [29], and two-dimensional nanosheets [30], [31], and so forth, permits extra environment friendly utilization of energetic websites. Hole mesoporous carbon spheres (HMCS) are outfitted with a excessive particular space and a wealthy pore construction [32], [33], enabling enhanced publicity of energetic websites for elevated adsorption of catalytic substrates. Moreover, the hole mesoporous construction can also accommodate massive quantities of small molecule substances, similar to CaO2, enhancing the focus of catalytic substrates (H2O2 or O2) [34]. Taken collectively, setting up atomically dispersed metallic energetic websites on HMCS generally is a promising path to additional improve the catalytic actions of DAzymes for reaching excessive catalytic remedy.
Though the catalytic effectivity of DAzyme is principally affected by the twin metallic atom and the nanocarrier, the impact of response temperature continues to be not negligible within the numerous catalytic processes [35], [36]. Not too long ago, many research have proven that increased temperature contributes to the rise within the catalytic actions of SAzymes [26], [27], [37]. The explanations behind the phenomenon could be attributed to the next factors. Firstly, in accordance with the Arrhenius equation, the response price fixed is exponentially associated to the temperature [38], [39], i.e., the catalytic response price enhances considerably with rising temperature. Moreover, temperature modifications can have an effect on the selectivity of the catalyst, which can select totally different response pathways at totally different temperatures, resulting in modifications in resultant selectivity [40], [41]. Moreover, a rise in temperature can lower the activation power of the response to lift the response price, which could be defined that molecules at excessive temperatures have increased common energies and usually tend to overcome the power obstacles of the response [41], [42]. Due to this fact, for DAzymes utilized in most cancers catalytic remedy, triggering native hyperthermia at catalytic websites not solely has a great likelihood to boost the catalytic selectivity and catalytic effectivity on the tumor websites but additionally could cause thermal ablation of most cancers cells, which in the end realizes a synergistic impact between thermotherapy and catalytic remedy.
Even when, DAzyme with a well-designed service and correct catalytic temperature can effectively catalyze O2 and H2O2 to generate ROS within the tumor microenvironment (TME), together with hydroxyl radicals (•OH), singlet oxygen (1O2), and superoxide ions (•O2−), the low focus of catalytic substrates (H2O2 and O2) limits the additional enchancment of catalytic actions. CaO2, a protected stable inorganic peroxide, can decompose to concurrently launch O2 and H2O2 in touch with water and has been extensively utilized within the regulation of TME [43], [44]. At current, DAzymes nanosystems with simultaneous excessive catalytic actions, hypoxia aid, H2O2 complement, and thermal technology have been not often reported, which is extremely fascinating in synergistic remedy of hyperthermia and catalytic remedy. Due to this fact, the introduction of CaO2 into DAzyme-mediated catalytic system appears to carry nice promise for enhancing tumor catalytic remedy.
Herein, we elaborated and synthesized a self-reinforcing DAzyme catalytic system (CaO2@P-DAzyme), consisting of twin atom (Cu and Mn)-embedded N-doped HMCS with a loading of CaO2 and modification of polyethylene glycol (PEG) for intrinsic triple enzyme-like (POD, CAT, OXD) assisted tumor catalytic remedy (Scheme 1). Introducing a second Cu atom across the unique Mn atom endowed CaO2@P-DAzyme with increased electron density and decrease H2O2 absorption power than SAzymes-Cu or SAzymes-Mn, realizing enhanced catalytic actions for most cancers remedy. Furthermore, the hole mesoporous construction obtained the publicity of extra energetic websites, and thus better adsorption of H2O2 or O2, additional enhancing the catalytic actions of CaO2@P-DAzyme. Moreover, loaded CaO2 within the cavity enabled H2O2 self-supplement and hypoxia aid, as soon as once more amplifying the triple enzyme-like actions. In the end, the PEG modification entrusted to CaO2@P-DAzyme excessive biocompatibility and long-term in vivo circulation. Surprisingly, the excessive photothermal conversion effectivity (51.95 %) of CaO2@P-DAzyme was found within the near-infrared-II area (NIR-II) window, which induced the native hyperthermia to additional reinforce the catalytic effectivity of the twin energetic websites. General, the inherent hole mesoporous construction, loading of CaO2, and NIR-II (1064 nm) irradiation can considerably improve the catalytic actions of CaO2@P-DAzyme, thus producing plentiful ROS and sharp rise of native temperature to attain glorious synergistic impact of PTT and catalytic remedy, which gives a novel technique to develop nano-catalysts with excessive actions for most cancers remedy.
