Nanocatalytic Tumor Therapy Research Articles

Two-Dimensional MoS2 nanosheets as cocatalyst to augment the nanocatalytic tumor therapy

As an appealing modality of tumor nanocatalytic therapeutics, Fenton chemistry has been extensively employed to combat cancer through the generation of highly cytotoxic reactive oxygen species (ROS). For iron-triggered catalytic Fenton chemistry, the therapeutic consequence was largely dependent on the available catalytically active ferrous species. In this work, hydrothermally synthesized molybdenum disulfide (MoS2-PEG) nanosheets were served as Fenton cocatalyst to enhance the Fenton kinetics as contributed by ultrasmall gallic acid (GA)-coordinated Fe nanoparticles (GA-Fe NPs) in tumor destruction. The tetravalent Mo4+ species of MoS2-PEG cocatalysts could efficiently transfer Fe3+ species into Fe2+ species by the reduction process, regenerating the catalytically active Fe2+ species and restoring the catalytic activity of GA-Fe nanocatalysts during the Fenton-based tumor therapeutics. Based on systematic in vitro and in vivo investigations of cocatalyst-augmented Fenton nanotherapeutics against 4-T1 tumor cells/xenografts, we have demonstrated a proof-of-concept enhanced nanocatalytic tumor-therapeutic modality by MoS2-PEG/GA-Fe nanocatalyst/cocatalyst hybridized system, which offers an explicit cocatalytic strategy to improve the therapeutic efficacy during nanocatalytic tumor therapy.

A pH-responsive single-atom nanozyme for photothermal-augmented nanocatalytic tumor therapy

Based on the physiological conditions of the tumor microenvironment (TME), many effective therapeutic strategies have been reported by using nanocatalysts. The main challenge is the insufficient catalytic activity of nanocatalysts within the acidic TME, significantly constraining their therapeutic efficacy. Herein, a pH-responsive bifunctional platform is developed with multiple enzyme-like catalytic activities for synergistic tumor therapy by integrating Rh single atoms nanozymes (SA-Rh nanozymes) with photothermal therapy (PTT). The SA-Rh nanozymes display peroxidase-mimicking activities within tumor cells, inducing a synergistic effect of enhanced reactive oxygen species generation for collaborative cancer therapy involving both chemodynamic therapy and PTT. Additionally, SA-Rh nanozymes exhibit catalase mimicking activities, enabling the generation of oxygen, and facilitating efficient nanozyme catalytic therapy in a substrate-cycle manner. Moreover, the catalytic efficiency of SA-Rh nanozymes is found to be higher under weak acidic conditions (pH=6.0) compared to neutral conditions (pH=7.4), thereby enabling the maintenance of catalytic activity in an acidic environment. The incorporation of this feature enhances its catalytic activity within the TME, optimizing the efficacy of nanozyme. The remarkable near-infrared I region absorption capability confers SA-Rh nanozymes with exceptional PTT performance, achieving an impressive efficiency of 34.1 %. Therefore, the SA-Rh nanozymes exhibit a remarkable ability to induce apoptosis in cancer cells through synergistic CDT and PTT modalities, effectively overcoming the shortcomings of current nanozyme catalytic therapy.

Oxidase-like manganese oxide nanoparticles: a mechanism of organic acids/aldehydes as electron acceptors and potential application in cancer therapy.

Identifying the underlying catalytic mechanisms of synthetic nanocatalysts or nanozymes is important in directing their design and applications. Herein, we revisited the oxidation process of 4,4'-diamino-3,3',5,5'-tetramethylbiphenyl (TMB) by Mn3O4 nanoparticles and revealed that it adopted an organic acid/aldehyde-triggered catalytic mechanism at a weakly acidic or neutral pH, which is O2-independent and inhibited by the pre-addition of H2O2. Importantly, similar organic acid/aldehyde-mediated oxidation was applied to other substrates of peroxidase in the presence of nanoparticulate or commercially available MnO2 and Mn2O3 but not MnO. The selective oxidation of TMB by Mn3O4 over MnO was further supported by density functional theory calculations. Moreover, Mn3O4 nanoparticles enabled the oxidation of indole 3-acetic acid, a substrate that can generate cytotoxic singlet oxygen upon single-electron transfer oxidation, displaying potential in nanocatalytic tumor therapy. Overall, we revealed a general catalytic mechanism of manganese oxides towards the oxidation of peroxidase substrates, which could boost the design and various applications of these manganese-based nanoparticles.

Catechol‐Isolated Atomically Dispersed Nanocatalysts for Self‐Motivated Cocatalytic Tumor Therapy

AbstractNanocatalytic tumor therapy based on Fenton nanocatalysts has attracted considerable attention because of its therapeutic specificity, enhanced outcomes, and high biocompatibility. Nevertheless, the rate‐determining step in Fenton chemistry, which involves the transition of a high‐valence metallic center (FeIII) to a Fenton‐active low‐valence metallic center (FeII), has hindered advances in nanocatalyst‐based therapeutics. In this study, we constructed mesoporous single iron atomic nanocatalysts (mSAFe NCs) by employing catechols from dopamine to coordinate and isolate single iron atoms. The catechols also serve as reductive ligands, generating a field‐effect‐based cocatalytic system that instantly reduces FeIII species to FeII species within the mSAFe NCs. This self‐motivated cocatalytic strategy enabled by mSAFe NCs accelerates the kinetics of the Fenton catalytic reaction, resulting in remarkable performance for nanocatalytic tumor therapy both in vitro and in vivo.

Catechol-Isolated Atomically Dispersed Nanocatalysts for Self-Motivated Cocatalytic Tumor Therapy.

Nanocatalytic tumor therapy based on Fenton nanocatalysts has attracted considerable attention because of its therapeutic specificity, enhanced outcomes, and high biocompatibility. Nevertheless, the rate-determining step in Fenton chemistry, which involves the transition of a high-valence metallic center (FeIII ) to a Fenton-active low-valence metallic center (FeII ), has hindered advances in nanocatalyst-based therapeutics. In this study, we constructed mesoporous single iron atomic nanocatalysts (mSAFe NCs) by employing catechols from dopamine to coordinate and isolate single iron atoms. The catechols also serve as reductive ligands, generating a field-effect-based cocatalytic system that instantly reduces FeIII species to FeII species within the mSAFe NCs. This self-motivated cocatalytic strategy enabled by mSAFe NCs accelerates the kinetics of the Fenton catalytic reaction, resulting in remarkable performance for nanocatalytic tumor therapy both in vitro and in vivo.

Supramolecular Nanozyme System Based on Polydopamine and Polyoxometalate for Photothermal-Enhanced Multienzyme Cascade Catalytic Tumor Therapy.

The advent of enzyme-facilitated cascade events in which endogenous substrates within the human body are used to generate reactive oxygen species (ROS) has spawned novel cancer treatment possibilities. In this study, a supramolecular cascade catalytic nanozyme system was successfully developed, exhibiting photothermal-enhanced multienzyme cascade catalytic and glutathione (GSH) depletion activities and ultimately triggering the apoptosis-ferroptosis synergistic tumor therapy. The nanozyme system was fabricated using β-cyclodextrin-functionalized polydopamine (PDA) as the substrate, which was then entangled with polyoxometalate (POM) via electrostatic forces and assembled with adamantane-grafted hyaluronic acid and glucose oxidase (GOx) via host-guest supramolecular interaction for tumor targeting and GOx loading. The catalytic function of GOx facilitates the conversion of glucose to H2O2 and gluconic acid. In turn, this process affirms the propitious generation of hydroxyl radical (•OH) through the POM-mediated cascade catalysis. Additionally, the POM species actively deplete the intracellular GSH pool, initiating a cascade catalytic tumor therapy. In addition, the PDA-POM-mediated photothermal hyperthermia boosted the cascade catalytic effect and increased ROS production. This confers considerable promise for photothermal therapy (PTT)/nanocatalytic cancer therapy on supramolecular nanozyme systems. The in vitro and in vivo antitumor efficacy studies demonstrated that the supramolecular cascade catalytic nanozyme system was effective at reducing tumor development while maintaining an acceptable level of biocompatibility. Henceforth, this study is to widen the scope of cascade catalytic nanoenzyme production using supramolecular techniques, as well as endeavor to delineate a prospective pathway for the application of PTT-enhanced nanocatalytic tumor therapy.

Mild-temperature responsive nanocatalyst for controlled drug release and enhanced catalytic therapy

Owing to the advantages of the in situ production of toxic agents through catalytic reactions, nanocatalytic therapy has arisen as a highly potential strategy for cancer therapeutics in recent years. However, the insufficient amount of endogenous hydrogen peroxide (H2O2) in the tumor microenvironment commonly limits their catalytic efficacy. Here, we employed carbon vesicle nanoparticles (CV NPs) with high near-infrared (NIR, 808 nm) photothermal conversion efficiency as carriers. Ultrafine platinum iron alloy nanoparticles (PtFe NPs) were grown in situ on the CV NPs, where the highly porous nature of the resultant CV@PtFe NPs was employed to encapsulate a drug, β-lapachone (La), and phase-change material (PCM). As a multifunctional nanocatalyst CV@PtFe/(La-PCM) NPs can exhibit a NIR-triggered photothermal effect and activate cellular heat shock response, which upregulates the downstream NQO1 via HSP70/NQO1 axis to facilitate bio-reduction of the concurrently melted and released La. Moreover, sufficient oxygen (O2) is supplied by CV@PtFe/(La-PCM) NPs catalyzed at the tumor site to reinforce the La cyclic reaction with abundant H2O2 generation. This promotes the bimetallic PtFe-based nanocatalysis, which breaks H2O2 down into highly toxic hydroxyl radicals (•OH) for catalytic therapy. Our results show that this multifunctional nanocatalyst can be used as a versatile synergistic therapeutic agent with NIR-enhanced nanocatalytic tumor therapy by tumor-specific H2O2 amplification and mild-temperature photothermal therapy, which holds promising potential for targeted cancer treatment. Statement of significanceWe present a multifunctional nanoplatform with mild-temperature responsive nanocatalyst for controlled drug release and enhanced catalytic therapy. This work aimed at not only reduce the damage to normal tissues caused by photothermal therapy, but also improves the efficiency of nanocatalytic therapy by stimulating endogenous H2O2 production through photothermal heat. In vitro and in vivo confirmed that CV@PtFe/(La-PCM) NPs exhibited powerful and overall antitumor effects. This formulation may provide an alternative strategy for the development of the mild- photothermal enhanced nanocatalytic therapy effect in solid tumor.

Biomimetic single-atom nanozyme system for efficient inhibition of gastric cancer ascites via SO2 gas-enhanced nanocatalytic cancer therapy

Peritoneal metastasis is a frequent cause of death in gastric cancer, and it is newer mainly treated by hyperthermic intraperitoneal chemotherapy (HIPEC),whereas the patients experience serious side effects.Thus it is urgent to develop new alternatives, one example being Cu single-atom nanozymes (SAZ) with peroxidase (POD)-like activity and which have good nanocatalytic tumor therapy (NCT) capabilities. A previously described approach was used to produce platelet membrane vesicles (PV) and Cu SAZ. However, insufficient hydrogen peroxide (H2O2) limit NCT effects. Therefore, to overcome these limitations, through physical extrusion, an SO2 prodrug (benzothiazole sulfinate, BTS) and Cu SAZ were combined with PV to create PSB. BTS were able to release SO2 before inducing SO3− that can cause cell apoptosis. In addition, it can also down-regulate glutathione (GSH) while up-regulating H2O2 to significantly improve the catalytic ability of Cu SAZ. This study proved that PSB could suppress over 90% of the tumor while displaying good tumor-targeting abilities alongside great biocompability. Thus, by innovatively combining gas therapy with NCT, the system developed in this study not only provide a new strategy for addressing peritoneal metastasis of gastric cancer, but also offers useful insights into designing a new generation of cancer therapy for potential clinical applications.

Disrupting Intracellular Iron Homeostasis by Engineered Metal‐Organic Framework for Nanocatalytic Tumor Therapy in Synergy with Autophagy Amplification‐Promoted Ferroptosis

AbstractMetal‐organic frameworks (MOFs) featuring good biocompatibility and tunable microstructures are developed to generate reactive oxygen species (ROS) for nanocatalytic therapy. However, the relatively low catalytic activity of MOF and intracellular ion homeostasis, a self‐protective mechanism to resist the intracellular accumulation of metal ions, results in the undesirable efficacy of tumor therapy. Herein, a therapeutic strategy is introduced of breaking intracellular iron homeostasis for nanocatalytic therapy in synergy with autophagy amplification‐promoted ferroptosis, based on etched MOF nanocatalyst (denoted COS@MOF), which is self‐etched by thiamine pyrophosphate (TPP) and further modified with autophagy agonist chitosan oligosaccharides (COS). Such self‐etched MOF exhibit an open cavity structure that is more conducive to adsorbing reactive molecules and producing more active sites, and an enhanced Fe(II)/Fe(III) ratio, reinforcing catalytic activity for ROS generation. The catalytic process of COS@MOF can be accelerated by overexpressed endogenous hydrogen sulfide (H2S) within colorectal tumors which reduces Fe3+ into more active Fe2+. In vitro and in vivo results demonstrate that COS@MOF amplifies autophagy to break iron homeostasis for facilitating ROS production to promote ferroptosis, achieving synergetic nanocatalytic/ferroptosis tumor therapy. This study provides a promising paradigm to elevate MOF‐based catalytic performance in synergy with autophagy amplification‐promoted ferroptosis for enhanced therapeutic efficacy.

Carbon nanosphere based bifunctional oxidoreductase nano-catalytic agent to mitigate hypoxia in cancer cells

Developing metal-free carbon nanozyme for tumor hypoxia is difficult. In biomedical applications, especially in the case of biomolecular detection, extensive research has been done on nanozymes with enzyme-mimicking catalytic activity. However, there are considerably fewer investigations on targeted nano-catalytic tumor therapy. Nano catalytic medicine-enabled chemotherapy is a safe and promising treatment strategy that involves the conversion of excess H2O2 into O2 in a tumor environment. Here we have synthesized carbon nanosphere (CNS) using the Camellia sinensis plant (CS-CNS). Further surface functionalization was achieved via nitrilotriacetic acid conjugation (NTA@CS-CNS). A stability study of synthesized nanozyme in the presence of various cations, anions, and 5 different pH range suggested the robustness of carbon based nanoassembly. The catalytic in vitro study shows that NTA@CS-CNS mimics peroxidase and catalase using TMB and H2O2 as substrates. NTA@CS-CNS showed Km and Vmax values of ~ 193.2 μM and 0.43 μM/s, ~ 413 μM and 1.42 μM/s, and ~ 378 μM and 1.63 μM/s, respectively when H2O2 and TMB was used for CAT and POD activity. Results showed that NTA@CS-CNS in combination with SFN and laser irradiation reduces hypoxia. Hence, our study could pave the path for the development of different non-toxic nano catalytic therapy for tumors in cancerous cells.

Bioinspired nanocatalytic tumor therapy by simultaneous reactive oxygen species generation enhancement and glutamine pathway-mediated glutathione depletion.

An insufficient intracellular H2O2 level and overexpressed glutathione (GSH) are still the major challenges for effective chemodynamic therapy (CDT). Inspired by the unique glutamine metabolism pathway in cancer cells, herein, intelligent nanocatalytic theranostics is used to enhance intracellular reactive oxygen species (ROS) accumulation via the production of H2O2 by a biomimetic nanozyme, and simultaneously reduce ROS consumption via the depression of GSH synthesis by the glutamine metabolic inhibitor. In this reactor, nano-sized Au and Fe3O4 coloaded dendritic mesoporous silica nanoparticles (DMSN-Au-Fe3O4) serve as the bifunctional nanozyme, where intracellular glucose is catalyzed into H2O2 by the glucose oxidase-mimicking Au nanoparticles and then immediately transformed into ˙OH by the peroxidase-like Fe3O4 nanoparticles. Then, CB839, the glutaminase (GLS) inhibitor, is grafted on the nanozyme, blocking the glutamine pathway and GSH biosynthesis. As a result, the as-designed nanoplatform with a three-pronged integration of Au-mediated H2O2 self-supply, Fe3O4-triggered Fenton-like reaction, and glutamine pathway-mediated GSH depletion significantly boosts the CDT efficacy, achieving remarkable and specific antitumor properties both in vitro and in vivo. This work not only paves a new way for rationally designing multi-functional nanozymes for achieving high therapeutic efficacy, but also provides new insights into the construction of bioinspired synergetic therapy by combining CDT and a key anticancer pathway.

Precisely designed Fex (x = 1-2) cluster nanocatalysts for effective nanocatalytic tumor therapy.

Atomically dispersed metal clusters are considered as promising nanocatalysts due to their excellent physicochemical properties. Here, we report a novel strategy for precisely designing Fex (x = 1-2) cluster nanocatalysts (Fe1-N-C and Fe2-N-C) with dual catalytic activity, which can catalyze H2O2 into reactive oxygen species (ROS) and oxidize glutathione (GSH) into glutathione disulfide simultaneously. The adsorption energies of Fe-N sites in Fe2-N-C for GSH and H2O2 intermediates were well controlled due to the orbital modulation of adjacent Fe sites, contributing to the higher dual catalytic activity compared to Fe1-N-C. Additionally, tamoxifen (TAM) was loaded into Fe2-N-C (Fe2@TDF NEs) to down-regulate the intracellular pH for higher Fenton-like catalytic efficiency and ROS production. The generated ROS could induce apoptosis and lipid peroxidation, triggering ferroptosis. Meanwhile, upregulation of ROS and lipid peroxidation, along with GSH depletion and GPX4 downregulation could promote the apoptosis and ferroptosis of tumor cells. In addition, the lactic acid accumulation effect of TAM and the high photothermal conversion ability of Fe2@TDF NEs could further enhance the catalytic activity to achieve synergistic antitumor effects. As a result, this work highlights the critical role of adjacent metal sites at the atomic-level and provides a rational guidance for the design and application of nanocatalytic antitumor systems.

Targeting acidogenic metabolism by engineering self-catalytic siRNA nanocarriers/nanocatalysts for amplified tumor apoptosis/ferroptosis

Nanocatalytic medicine holds great potential in inhibiting tumor progression based on the synergistic catalytic production of toxic reactive oxygen species (ROS) between fenton nanoagents and tumor-specific endogenous substances. However, the cellular self-antioxidant and detoxification mechanisms result in discounted cell killing effect of nanocatalytic therapeutics. In this work, we design and engineer an intelligent bimetallic-type metal-organic framework (MOF) nanosystem that facilitates efficient gene delivery and expression, consequently enabling dual regulation of intracellular acid metabolism and significant amplification of nanocatalytic tumor therapy through enhanced elicitation of apoptosis and ferroptosis. The endogenous RNA interference and exogenous acidic substances supplement concurrently elevated the intracellular acidity and amplified the nanocatalytic reactions-induced ferroptosis. Especially, the reduced intracellular pH-derived calcium influx caused mitochondrial calcium overload, rendering cancer cells highly susceptible to nanocatalysts-triggered oxidative stress apoptotic damage, resulting in significantly synergistic tumor suppression. This work demonstrates the concept of amplified ferroptosis/apoptosis induced by self-enhancing intelligent nanocatalytic tumor treatment through simultaneously co-targeting two specific cancer hallmarks.

Copper-olsalazine metal-organic frameworks as a nanocatalyst and epigenetic modulator for efficient inhibition of colorectal cancer growth and metastasis

Despite the extensive explorations of nanoscale metal−organic frameworks (nanoMOFs) in drug delivery, the intrinsic bioactivity of nanoMOFs, such as anticancer activity, is severely underestimated owing to the overlooked integration of the hierarchical components including nanosized MOFs and molecular-level organic ligands and metal-organic complexes. Herein, we propose a de novo design of multifunctional bioactive nanoMOFs ranging from molecular to nanoscale level, and demonstrate this proof-of-concept by a copper−olsalazine (Olsa, a clinically approved drug for inflammatory bowel disease, here as a bioactive linker and DNA hypomethylating agent) nanoMOF displaying a multifaceted anticancer mechanism: (1) Cu-Olsa nanoMOF-mediated redox dyshomeostasis for enhanced catalytic tumor therapy, (2) targeting downregulation of cyclooxygenase-2 by the organic complex of Cu2+ and Olsa, and (3) Olsa-mediated epigenetic regulation. Cu-Olsa nanoMOF displayed an enzyme-like catalytic activity to generate cancericidal species ·OH and 1O2 from rich H2O2 in tumors, improved the expression of tumor suppressors TIMP3 and AXIN2 by epigenetic modulation, and fulfilled selective inhibition of colorectal cancer cells over normal cells. The hyaluronic acid-modified nanoMOF further verified the efficient suppression of CT26 colorectal tumor growth and metastasis in murine models. Overall, these results suggest that Olsa-based MOF presents a platform of epigenetic therapy-synergized nanomedicine for efficient cancer treatment and provides a powerful strategy for the design of intrinsically bioactive nanoMOFs. Statement of significanceMetal−organic frameworks (MOFs) with intrinsic bioactivities such as anticancer and antibacterial activity are of great interest. Herein, we reported a bioactive copper−olsalazine (Cu-Olsa) nanoMOF as a nanodrug for colorectal cancer treatment. This nanoMOF per se displayed enzyme-like catalytic activity to generate cancericidal species ·OH and 1O2 from rich H2O2 in tumors for nanocatalytic tumor therapy. Upon dissociation into small molecular copper-organic complex and olsalazine in cancer cells, COX-2 inhibition and epigenetic modulation were fulfilled for selective inhibition of colorectal cancer growth and metastasis.

Photo-enhanced upcycling H2O2 into hydroxyl radicals by IR780-embedded Fe3O4@MIL-100 for intense nanocatalytic tumor therapy

Reactive oxygen species (ROS)-based nanocatalytic tumor therapy is alluring owing to the capability to generate highly cytotoxic ∙OH radicals from tumoral H2O2. However, the antitumor efficacy is highly dependent on the radical generation efficiency and challenged by the high levels of antioxidative glutathione (GSH) in cancer cells. Herein, we report an IR-780 decorated, GSH-depleting Fe3O4@MIL-100 (IFM) nanocomposite for photo-enhanced tumor catalytic therapy by extensive production of ∙OH, which is realized by an integration of excellent peroxidase-like activity of IFM, selective upregulation of tumoral H2O2 by β-lapachone, and localized hyperthermia by near infrared light irradiation. IFM shows potentiated antiproliferative effect in 4T1 cancer cells by ∙OH overproduction and glutathione scavenging, inducing intracellular redox dyshomeostasis and cell death by concurrent apoptosis and ferroptosis. In vivo antitumor investigation further demonstrates photoacoustic and fluorescence imaging-guided combinational therapy with a tumor inhibition rate of 96.4%. This study provides a strategy of photo-enhanced nanocatalytic tumor therapy by tumor-specific H2O2 amplification and hyperthermia.

Cu‐Doped Polypyrrole with Multi‐Catalytic Activities for Sono‐Enhanced Nanocatalytic Tumor Therapy (Small 29/2022)

Cu‐Doped Polypyrrole with Multi‐Catalytic Activities for Sono‐Enhanced Nanocatalytic Tumor Therapy (Small 29/2022)

Injectable Hydrogel System for Camptothecin Initiated Nanocatalytic Tumor Therapy With High Performance.

Single photothermal therapy (PTT) has many limitations in tumor treatments. Multifunctional nanomaterials can cooperate with PTT to achieve profound tumor killing performance. Herein, we encapsulated chemotherapeutic drug camptothecin (CPT) and pyrite (FeS2) with dual enzyme activity (glutathione oxidase (GSH-OXD) and peroxidase (POD) activities) into an injectable hydrogel to form a CFH system, which can improve the level of intratumoral oxidative stress, and simultaneously realize FeS2-mediated PTT and nanozymes catalytic treatment. After laser irradiation, the hydrogel gradually heats up and softens under the photothermal agent FeS2. The CPT then released from CFH to tumor microenvironment (TME), thereby enhancing the H2O2 level. As a result, FeS2 can catalyze H2O2 to produce ·OH, and cooperate with high temperature to achieve high-efficiency tumor therapy. It is worth noting that FeS2 can also deplete excess glutathione (GSH) in the cellular level, further amplifying oxidative stress. Both in vivo and in vitro experiments show that our CFH exhibits good tumor-specific cytotoxicity. The CFH we developed provides new insights for tumor treatment.

Cu-Doped Polypyrrole with Multi-Catalytic Activities for Sono-Enhanced Nanocatalytic Tumor Therapy.

Nanocatalytic medicine is a burgeoning disease treatment model with high specificity and biosafety in which the nanocatalyst is the core of driving catalytic reaction to generate therapeutic outcomes. However, the robust defense systems in the pathological region would counteract nanocatalyst-initiated therapeutics. Here, a Cu-doped polypyrrole is innovatively developed by a facile oxidative polymerization reaction, which exhibits intriguing multi-catalytic activities, including catalyzing H2 O2 to generate O2 and · OH, and consuming reduced glutathione by a Cu(II)-Cu(I) transition approach. By decorating with sonosensitizers and DSPE-PEG, the obtained CuPPy-TP plus US irradiation can induce severe oxidative damage to tumor cells by amplifying oxidative stress and simultaneously relieving antioxidant capacity in tumors based on the highly effective sonochemical and redox reactions. The notable tumor-specific biodegradability, remarkable cell apoptosis in vitro, and tumor suppression in vivo are demonstrated in this work, which not only present a promising biocompatible antitumor nanocatalyst but also broaden the perspective in oxidative stress-based antitumor therapy.

Novel Strategy for Optimized Nanocatalytic Tumor Therapy: From an Updated View

Nanozyme has been experiencing rapid development in biomedical applications involving biosensors, immunoassays, and antitumor agents in recent years due to its tunable catalytic performance and desirable biocompatibility. Since the first exploration of nanozyme‐based Fenton reaction for nanocatalytic therapy (NCT) against tumor, a variety of Fenton (and Fenton‐like) nanozymes, such as Fe3O4, transition metal ions (Co2+, Cu2+, and Mn2+), and metal–organic frameworks (MOFs), have been proved as desirable candidates for tumor therapy, and the modulation of the tumor microenvironment (TME) is determined to be a feasible approach to improve the catalytic efficiency for in situ tumor suppression. At present, increasing studies have focused on improving the therapeutic efficiency of NCT by formulating multifunctional nanozyme‐based systems to satisfy the demand for versatile and optimized applications. Herein, updated insights into the novel strategies of 1) achieving highly effective nanocatalytic reactions, including the modification of nanocatalysts and TME‐modulating approaches, are provided and 2) the design and formulation of multifunctional nanozyme‐based systems which achieve targeted, synergistic therapy, and theranostic applications are analyzed and concluded. Concise and concentrated comments and outlooks are illuminated at the end to outline the perspectives and the remaining challenges for the next‐step explorations on further biomedical translation of NCT.

Biomimetic copper single-atom nanozyme system for self-enhanced nanocatalytic tumor therapy

Biomimetic copper single-atom nanozyme system for self-enhanced nanocatalytic tumor therapy