Gold Nanoparticles in Parkinson's Disease Therapy: A Focus on Plant-Based Green Synthesis.

Parkinson's disease (PD) is a progressive neurodegenerative disease that affects approximately 1% of people over the age of 60 and 5% of those over the age of 85. Current drugs for Parkinson's disease mainly affect the symptoms and cannot stop its progression. Nanotechnology provides a solution to address some challenges in therapy, such as overcoming the blood-brain barrier (BBB), adverse pharmacokinetics, and the limited bioavailability of therapeutics. The reformulation of drugs into nanoparticles (NPs) can improve their biodistribution, protect them from degradation, reduce the required dose, and ensure target accumulation. Furthermore, appropriately designed nanoparticles enable the combination of diagnosis and therapy with a single nanoagent. In recent years, gold nanoparticles (AuNPs) have been studied with increasing interest due to their intrinsic nanozyme activity. They can mimic the action of superoxide dismutase, catalase, and peroxidase. The use of 13-nm gold nanoparticles (CNM-Au8®) in bicarbonate solution is being studied as a potential treatment for Parkinson's disease and other neurological illnesses. CNM-Au8® improves remyelination and motor functions in experimental animals. Among the many techniques for nanoparticle synthesis, green synthesis is increasingly used due to its simplicity and therapeutic potential. Green synthesis relies on natural and environmentally friendly materials, such as plant extracts, to reduce metal ions and form nanoparticles. Moreover, the presence of bioactive plant compounds on their surface increases the therapeutic potential of these nanoparticles. The present article reviews the possibilities of nanoparticles obtained by green synthesis to combine the therapeutic effects of plant components with gold.

Multifunctional Two-Dimensional Bi2Se3 nanodisks as a Non-Inflammatory photothermal agent for glioma treatment.

Photothermal therapy (PTT) has gained widespread attention due to its significant advantages, such as noninvasiveness and ability to perform laser localization. However, PTT usually reaches temperatures exceeding 50 °C, which causes tumor coagulation necrosis and unfavorable inflammatory reactions, ultimately decreasing its efficacy. In this study, multifunctional two-dimensional Bi2Se3 nanodisks were synthesized as noninflammatory photothermal agents for glioma therapy. The Bi2Se3 nanodisks showed high photothermal stability and biocompatibility and no apparent toxicology. In addition, in vitro and in vivo studies revealed that the Bi2Se3 nanodisks effectively ablated gliomas at relatively low concentrations and inhibited tumor proliferation and migration. Moreover, the multienzymatic activity of the Bi2Se3 nanodisks inhibited the PTT-induced inflammatory response through their high ability to scavenge reactive oxygen species. Finally, the Bi2Se3 nanodisks demonstrated computed tomography capabilities for integrating diagnosis and treatment. These findings suggest that multifunctional Bi2Se3 nanodisk nanozymes can enable more effective cancer therapy and noninflammatory PTT.

Cationic regulation of specificity and activity of defective MCo2O4 nanozyme (M=Fe, Co, Ni, Cu) for colorimetric detection of caffeic acid.

Spinel oxide has great promise in constructing highly active nanozymes due to its tunable crystal structure. However, it still faces the problems of poor specificity and insufficient enzyme activity, which limits its application in the field of analysis. Herein, a series of transition metal spinel oxides were synthesized by cation regulation strategy, and their enzymatic activity and catalytic mechanism were analyzed. Interestingly, FeCo2O4, Co3O4 and NiCo2O4 had oxidase-like activity and peroxidase-like activity, while CuCo2O4 had specific and high oxidase-like activity. Their oxidase-like activities follow the order of FeCo2O4 < Co3O4 < NiCo2O4 < CuCo2O4, which is consistent with their cation radius. The smaller the cation radius of tetrahedral site, the more beneficial it is to increase the oxidase-like activity. The high oxidase-like activity of CuCo2O4 may be attributed to the production of 1O2, •O2- and •OH. EPR results showed the presence of abundant oxygen vacancies in CuCo2O4. Upon the introduction of EDTA, TMB color reaction fades because of oxygen vacancies elimination by EDTA, indicating that oxygen vacancies played an important role in the reaction. Based on the inhibition effect of caffeic acid on the high oxidase-like activity of CuCo2O4, a simple and sensitive caffeic acid colorimetric sensing platform was developed. The linear range for the detection of caffeic acid is 0.02-15 µM, with a detection limit as low as 13 nM. The constructed sensor enables the detection of caffeic acid in caffeic acid tablets and actual water samples, providing a new strategy for the detection of caffeic acid and drug quality control.

Integrated Computational and Experimental Framework for Inverse Screening of Candidate Antibacterial Nanomedicine.

Nanomedicine is promising for disease prevention and treatment, but there are still many challenges that hinder its rapid development. A major challenge is to efficiently seek candidates with the desired therapeutic functions from tremendously available materials. Here, we report an integrated computational and experimental framework to seek alloy nanoparticles from the Materials Project library for antibacterial applications, aiming to learn the inverse screening concept from traditional medicine for nanomedicine. Because strong peroxidase-like catalytic activity and weak toxicity to normal cells are the desired material properties for antibacterial usage, computational screening implementing theoretical prediction models of catalytic activity and cytotoxicity is first conducted to select the candidates. Then, experimental screening based on scanning probe block copolymer lithography is used to verify and refine the computational screening results. Finally, the best candidate AuCu3 is synthesized in solution and its antibacterial performance over other nanoparticles against S. aureus and E. coli. is experimentally confirmed. The results show the power of inverse screening in accelerating the research and development of antibacterial nanomedicine, which may inspire similar strategies for other nanomedicines in the future.

A Mechanism Underpinning the Bioenergetic Metabolism-Regulating Function of Gold Nanocatalysts.

Bioenergetic deficits are known to be significant contributors to neurodegenerative diseases. Nevertheless, identifying safe and effective means to address intracellular bioenergetic deficits remains a significant challenge. This work provides mechanistic insights into the energy metabolism-regulating function of colloidal Au nanocrystals, referred to as CNM-Au8, that are synthesized electrochemically in the absence of surface-capping organic ligands. When neurons are subjected to excitotoxic stressors or toxic peptides, treatment of neurons with CNM-Au8 results in dose-dependent neuronal survival and neurite network preservation across multiple neuronal subtypes. CNM-Au8 efficiently catalyzes the conversion of an energetic cofactor, nicotinamide adenine dinucleotide hydride (NADH), into its oxidized counterpart (NAD+ ), which promotes bioenergy production by regulating the intracellular level of adenosine triphosphate. Detailed kinetic measurements reveal that CNM-Au8-catalyzed NADH oxidation obeys Michaelis-Menten kinetics and exhibits pH-dependent kinetic profiles. Photoexcited charge carriers and photothermal effect, which result from optical excitations and decay of the plasmonic electron oscillations or the interband electronic transitions in CNM-Au8, are further harnessed as unique leverages to modulate reaction kinetics. As exemplified by this work, Au nanocrystals with deliberately tailored structures and surfactant-free clean surfaces hold great promise for developing next-generation therapeutic agents for neurodegenerative diseases.

A Sonoresponsive and NIR-II-Photoresponsive Nanozyme for Heterojunction-Enhanced "Three-in-One" Multimodal Oncotherapy.

Although low-cost nanozymes with excellent stability have demonstrated the potential to be highly beneficial for nanocatalytic therapy (NCT), their unsatisfactory catalytic activity accompanied by intricate tumor microenvironment (TME) significantly hinders the therapeutic effect of NCT. Herein, for the first time, a heterojunction (HJ)-fabricated sonoresponsive and NIR-II-photoresponsive nanozyme is reported by assembling carbon dots (CDs) onto TiCN nanosheets. The narrow bandgap and mixed valences of Ti3+ and Ti4+ endow TiCN with the capability to generate reactive oxygen species (ROS) when exposed to ultrasound (US), as well as the dual enzyme-like activities of peroxidase and glutathione peroxidase. Moreover, the catalytic activities and sonodynamic properties of the TiCN nanosheets are boosted by the formation of HJs owing to the increased speed of carrier transfer and the enhanced electron-hole separation. More importantly, the introduction of CDs with excellent NIR-II photothermal properties could achieve mild hyperthermia (43 °C) and thereby further improve the NCT and sonodynamic therapy (SDT) performances of CD/TiCN. The synergetic therapeutic efficacy of CD/TiCN through mild hyperthermia-amplified NCT and SDT could realize "three-in-one" multimodal oncotherapy to completely eliminate tumors without recurrence. This study opens a new avenue for exploring sonoresponsive and NIR-II-photoresponsive nanozymes for efficient tumor therapy based on semiconductor HJs.

Pillar arene Se nanozyme therapeutic systems with dual drive power effectively penetrated mucus layer combined therapy acute lung injury.

siRNA has demonstrated a promising paradigm for therapy of acute lung injury(ALI). However, the pulmonary mucus layer barrier powerfully hinders the therapeutic efficacy. Herein, we proposed to use dual drive power to enhance the mucus permeation of siRNA by constructing the neutral and targeted selenium nanozymes therapeutic system. The multifunctional selenium nanozymes (CWP-Se@Man) were synthesized by modifying with cationic water-soluble pillar arene (CWP) and mannose (Man). After loading CCR2-siRNA, the CWP-Se@Man reached electroneutrality that co-driven by electroneutrality and targeting, the mucus permeation capacity of CWP-Se@Man enhanced by ∼15 fold, thus effectively penetrate pulmonary mucus layer and deliver CCR2-siRNA into macrophages. Moreover, with optimizing the composition of CWP-Se@Man made of CWP (Slutsky, 2013) [5] or CWP (Ichikado et al., 2012) [6], the therapeutic system CWP (Ichikado et al., 2012) [6]-Se@Man showed better biological activities due to smaller size. In inflamed modes, the CWP-Se@Man nanotherapeutic systems loading CCR2-siRNA not only exerted pronounced anti-inflammatory effect through combining inhibit the chemotactic effect and ROS, but also effectively against ALI after blocking the circulatory effect of ROS and inflammatory cytokines. Therefore, this strategy of dual-driving force penetration mucus renders a unique approach for mediating trans-mucus nucleic acid delivery in lungs, and provide a promising treatment for the acute lung injury therapy.

A Mild Hyperthermia Hollow Carbon Nanozyme as Pyroptosis Inducer for Boosted Antitumor Immunity.

The immune checkpoint blockade (ICB) antibody immunotherapy has demonstrated clinical benefits for multiple cancers. However, the efficacy of immunotherapy in tumors is suppressed by deficient tumor immunogenicity and immunosuppressive tumor microenvironments. Pyroptosis, a form of programmed cell death, can release tumor antigens, activate effective tumor immunogenicity, and improve the efficiency of ICB, but efficient pyroptosis for tumor treatment is currently limited. Herein, we show a mild hyperthermia-enhanced pyroptosis-mediated immunotherapy based on hollow carbon nanozyme, which can specifically amplify oxidative stress-triggered pyroptosis and synchronously magnify pyroptosis-mediated anticancer responses in the tumor microenvironment. The hollow carbon sphere modified with iron and copper atoms (HCS-FeCu) with multiple enzyme-mimicking activities has been engineered to induce cell pyroptosis via the radical oxygen species (ROS)-Tom20-Bax-Caspase 3-gasdermin E (GSDME) signaling pathway under light activation. Both in vitro and in vivo antineoplastic results confirm the superiority of HCS-FeCu nanozyme-induced pyroptosis. Moreover, the mild photothermal-activated pyroptosis combining anti-PD-1 can enhance antitumor immunotherapy. Theoretical calculations further indicate that the mild photothermal stimulation generates high-energy electrons and enhances the interaction between the HCS-FeCu surface and adsorbed oxygen, facilitating molecular oxygen activation, which improves the ROS production efficiency. This work presents an approach that effectively transforms immunologically "cold" tumors into "hot" ones, with significant implications for clinical immunotherapy.

A robust and facile colorimetric aptasensor for the detection of Salmonella Typhimurium based on the regulation of Fe3O4@Cu@PCPy yolk-shell nanozyme activity.

Due to their superparamagnetism and enzyme-like activity, iron oxide (Fe3O4) nanozymes can be readily used for sample pretreatment and the generation of detection signals, and have, thus, attracted much attention in the field of bioanalysis and diagnosis. However, the low catalytic activity of Fe3O4 nanozymes does reduce the sensitivity of Fe3O4-based methods, limiting their application. In this study, Fe3O4@Cu@poly(pyrrole-2-carboxylic acid) yolk-shell nanozymes (Fe3O4@Cu@PCPy YSNs) were synthesized using a facile approach and selective chemical etching technology. Compared with Fe3O4 nanozymes, the Fe3O4@Cu@PCPy YSNs demonstrated a three-fold increase in the peroxidase-like activity, good dispersity and strong superparamagnetism. In addition, the flower-shaped structure of aptamer-complementary strand (Apt-CS) conjugates was designed on the surface of the Fe3O4@Cu@PCPy YSNs, which effectively inhibited their peroxidase-like activity by creating a physical barrier that hindered the access of substrates to the center of the Fe3O4@Cu@PCPy YSNs. Based on this principle, a robust and facile colorimetric aptasensor was developed for detecting Salmonella Typhimurium. The flower-shaped Apt-CS were dissociated in the presence of S. Typhimurium, promoting the recovery of Fe3O4@Cu@PCPy YSN catalytic activity. Under optimized conditions, this proposed aptasensor successfully detected S. Typhimurium in a linear range of 3 to 3 × 106 CFU/mL, achieving a detection limit of 1 CFU/mL. Finally, the feasibility of this novel aptasensor was further validated by three actual samples, with recoveries of between 84.3% and 102%, thereby demonstrating the huge potential of the proposed aptasensor for detecting S. Typhimurium in foods.

Machine learning-guided the fabrication of nanozyme based on highly-stable violet phosphorene decorated with phosphorus-doped hierarchically porous carbon microsphere for portable intelligent sensing of mycophenolic acid in silage.

Violet phosphorene (VP) have been proved to be more stable than black phosphorene, but few reports for its application in electrochemical sensors. In this study, a highly-stable VP decorated with phosphorus-doped hierarchically porous carbon microsphere (PCM) with multiple enzyme-like activities as a nanozyme sensing platform for portable intelligent analysis of mycophenolic acid (MPA) in silage with machine learning (ML) assistance is successfully fabricated. The pore size distribution on the PCM surface is discussed using N2 adsorption tests, and morphological characterization indicates that the PCM is embedded in the layers of lamellar VP. The affinity of the VP-PCM nanozyme obtained under the guidance of the ML model reaches Km = 12.4 µmol/L for MPA. The VP-PCM/SPCE for the efficient detection of MPA exhibits high sensitivity, a wide detection range of 2.49 µmol/L - 71.14 µmol/L with a low limit of detection of 18.7 nmol/L. The proposed ML model with high prediction accuracy (R2 = 0.9999, MAPEP = 0.0081) assists the nanozyme sensor for intelligent and rapid quantification of MPA residues in corn silage and wheat silage with satisfactory recoveries of 93.33%-102.33%. The excellent biomimetic sensing properties of the VP-PCM nanozyme are driving the development of a novel MPA analysis strategy assisted by ML in the context of production requirements of livestock safety.

Colorimetric sensor array based on Au2Pt nanozymes for antioxidant nutrition quality evaluation in food.

Total antioxidant capacity (TAC) has become an important index to evaluate the food quality. Effective antioxidant detection has been the research hotspot of scientists. In this work, a novel three-channel colorimetric sensor array founded on Au2Pt bimetallic nanozymes for the discrimination of antioxidants in food was constructed. Benefiting from the unique bimetallic doping structure, Au2Pt nanospheres exhibited the excellent peroxidase-like activity with Km of 0.044 mM and Vmax of 19.37 × 10-8 M s-1 toward TMB. The density functional theory (DFT) calculation revealed that Pt atom in the doping system was active sites and there was no energy barrier in catalytic reaction which made Au2Pt nanospheres had excellent catalytic activity. Accordingly, a multifunctional colorimetric sensor array was constructed based on Au2Pt bimetallic nanozymes for rapid and sensitive detection of five antioxidants. Based on the different reduction ability of antioxidants, oxidized TMB could be reduced in different degrees. In the presence of H2O2, the colorimetric sensor array could generate differential colorimetric signals (fingerprints) by using TMB as the chromogenic substrate, which could be accurately discriminated through linear discriminant analysis (LDA) with a detection limit of <0.2 µM. The sensor array was able to the evaluate TAC in three actual samples (milk, green tea and orange juice). Furthermore, we prepared a rapid detection strip to meet the needs of practical application, making a positive contribution to food quality evaluation.

A Homing Missile-Like Nanotherapeutic with Single-Atom Catalytic Sites for In Situ Elimination of Intracellular Bacterial Pathogens.

Intracellular bacterial pathogens hiding in host cells tolerate the innate immune system and high-dose antibiotics, resulting in recurrent infections that are difficult to treat. Herein, a homing missile-like nanotherapeutic (FeSAs@Sa.M) composed of a single-atom iron nanozyme (FeSAs) core coated with infected macrophage membrane (Sa.M) is developed for in situ elimination of intracellular methicillin-resistant S. aureus (MRSA). Mechanically, the FeSAs@Sa.M initially binds to the extracellular MRSA via the bacterial recognition ability of the Sa.M component. Subsequently, the FeSAs@Sa.M can be transported to the intracellular MRSA-located regions in the host cell like a homing missile under the guidance of the extracellular MRSA to which it is attached, generating highly toxic reactive oxygen species (ROS) for intracellular MRSA killing via the enzymatic activities of the FeSAs core. The FeSAs@Sa.M is far superior to FeSAs in killing intracellular MRSA, proposing a feasible strategy for treating intracellular infections by in situ generating ROS in bacterial residing regions.

Construction of PEGylated chlorin e6@CuS-Pt theranostic nanoplatforms for nanozymes-enhanced photodynamic-photothermal therapy.

Multifunctional nanoagents with photodynamic therapy (PDT) and photothermal therapy (PTT) functions have shown great promise for cancer treatment, while the design and synthesis of efficient nanoagents remain a challenge. To realize nanozyme-enhanced PDT-PTT combined therapy, herein we have synthesized the Ce6@CuS-Pt/PEG nanoplatforms as a model of efficient nanoagents. Hollow CuS nanospheres with an average diameter of âˆ¼ 200 nm are first synthesized through vulcanization using Cu2O as the precursor. Subsequently, CuS nanospheres are surface-decorated with Pt nanoparticles (NPs) as nanozyme via an in-situ reduction route, followed by modifying the DSPE-PEG5000 and loading the photosensitizer Chlorin e6 (Ce6). The obtained Ce6@CuS-Pt/PEG NPs exhibit high photothermal conversion efficiency (43.08%), good singlet oxygen (1O2) generation ability, and good physiological stability. In addition, Ce6@CuS-Pt/PEG NPs show good catalytic performance due to the presence of Pt nanozyme, which can effectively convert H2O2 to O2 and significantly enhance the production of cytotoxic 1O2. When Ce6@CuS-Pt/PEG NPs dispersion is injected into mice, the tumors can be wholly suppressed owing to nanozyme-enhanced PDT-PTT combined therapy, providing better therapeutic effects compared to single-mode phototherapy. Thus, the present Ce6@CuS-Pt/PEG NPs can act as an efficient multifunctional nanoplatform for tumor therapy.

Biofilm Homeostasis Interference Therapy via 1 O2 -Sensitized Hyperthermia and Immune Microenvironment Re-Rousing for Biofilm-Associated Infections Elimination.

The recurrence of biofilm-associated infections (BAIs) remains high after implant-associated surgery. Biofilms on the implant surface reportedly shelter bacteria from antibiotics and evade innate immune defenses. Moreover, little is currently known about eliminating residual bacteria that can induce biofilm reinfection. Herein, novel "interference-regulation strategy" based on bovine serum albumin-iridium oxide nanoparticles (BIONPs) as biofilm homeostasis interrupter and immunomodulator via singlet oxygen (1 O2 )-sensitized mild hyperthermia for combating BAIs is reported. The catalase-like BIONPs convert abundant H2 O2 inside the biofilm-microenvironment (BME) to sufficient oxygen gas (O2 ), which can efficiently enhance the generation of 1 O2 under near-infrared irradiation. The 1 O2 -induced biofilm homeostasis disturbance (e.g., sigB, groEL, agr-A, icaD, eDNA) can disrupt the sophisticated defense system of biofilm, further enhancing the sensitivity of biofilms to mild hyperthermia. Moreover, the mild hyperthermia-induced bacterial membrane disintegration results in protein leakage and 1 O2 penetration to kill bacteria inside the biofilm. Subsequently, BIONPs-induced immunosuppressive microenvironment re-rousing successfully re-polarizes macrophages to pro-inflammatory M1 phenotype in vivo to devour residual biofilm and prevent biofilm reconstruction. Collectively, this 1 O2 -sensitized mild hyperthermia can yield great refractory BAIs treatment via biofilm homeostasis interference, mild-hyperthermia, and immunotherapy, providing a novel and effective anti-biofilm strategy.

Zero-Valence Selenium-Enriched Prussian Blue Nanozymes Reconstruct Intestinal Barrier against Inflammatory Bowel Disease via Inhibiting Ferroptosis and T Cells Differentiation.

The structural disruption of mechanical barrier and dysfunction of immune barrier in intestinal, are important factors, that aggravate inflammatory bowel disease (IBD). To tackle this challenge, a multifunctional nanozyme capable of scavenging reactive oxygen species (ROS) and inhibiting ferroptosis or T cells differentiation for IBD therapy is here reported. In this work, zero-valence selenium-enriched Prussian blue nanozymes (Se-HMPB nanozymes) are prepared via the hard template method. PB nanozymes with multi-enzyme activities can effectively scavenge various ROS in inflammatory tissues. Meanwhile, the presence of selenium element endows the glutathione peroxidase activity of Se-HMPB nanozymes, which can inhibit ferroptosis and reverse the lipid peroxidation of intestinal epithelial cells to protect the intestinal mechanical barrier in ulcerative colitis (UC) model. In addition, selenium supplementation can realize efficient inhibition on the differentiation of T cells in Crohn's disease (CD) model, regulating the intestinal immune barrier. Thus, the Se-HMPB nanozymes reconstructed intestinal barrier via inhibiting ferroptosis and T cells differentiation in UC and CD models, depicting great potential to alleviate IBD.

Label-free ultra-sensitive colorimetric detection of hepatitis E virus based on oxidase-like activity of MnO2 nanosheets.

Hepatitis E virus (HEV) is an evolving infectious entity that causes viral hepatitis infections worldwide. Current routine methods of identifying and diagnosing HEV are someway laborious and costly. Based on the biomimicking oxidase-like activity of MnO2 nanosheets, we designed a label-free, highly sensitive colorimetric sensing technique for HEV detection. The prepared MnO2 catalyst displays intrinsic biomimicking oxidase-like catalytic activity and efficiently oxidizes the 3,3',5,5'-tetramethylbenzidine (TMB) substrate from colorless to blue colored oxidized TMB (oxTMB) product which can be measured at 652 nm by UV-visible spectrum. When the HEV-DNA was added, DNA adsorbed easily on MnO2 surface through physical adsorption and electrostatic interaction which hinders the oxidase-like catalytic activity of MnO2. Upon the introduction of target, the HEV target DNA binds with its complementary ssDNA on the surface of MnO2, the hybridized DNA releases from the surface of MnO2, which leads to recovery of oxidase-like catalytic activity of MnO2. This strategy was applied to construct a colorimetric technique for HEV detection. The approach works in the linear range of 1 fM-100 nM DNA concentration with the limit of detection (LOD) of 3.26 fM (S/N = 3) and quantitative limit (LOQ) of 36.08 fM. The TMB-MnO2 platform was highly selective for HEV target DNA detection when compared with potential interferences. Result of serum sample analysis demonstrates that this sensing system can be used for clinical diagnostic applications.

Carbon Dot@MXene Nanozymes with Triple Enzyme-Mimic Activities for Mild NIR-II Photothermal-Amplified Nanocatalytic Therapy.

Nanozymes have shown promising potential in disease treatment owing to the advantages of low-cost, facile fabrication, and high stability. However, the highly complex tumor microenvironment (TME) and inherent low catalytic activity severely restrict the clinical applications of nanozymes. Herein, a novel mild hyperthermia-enhanced nanocatalytic therapy platform based on Z-scheme heterojunction nanozymes by depositing N-doped carbon dots (CDs) onto Nb2 C nanosheets is constructed. CD@Nb2 C nanozymes not only display outstanding photothermal effects in the safe and efficient NIR-II window but also possess triple enzyme-mimic activities to obtain amplified ROS levels. The triple enzyme-mimic activities and NIR-II photothermal properties of CD nanozymes are enhanced by the construction of Z-scheme heterojunctions owing to the accelerated carrier transfer process. More importantly, the introduction of mild hyperthermia can further improve the peroxidase-mimic and catalase-mimic activities as well as the glGSH depletion abilities of CD@Nb2 C nanozymes, thereby producing more ROS to efficiently inhibit tumor growth. The combined therapy effect of CD@Nb2 C nanozymes through mild NIR-II photothermal-enhanced nanocatalytic therapy can achieve complete tumor eradication. This work highlights the efficient tumor therapy potential of heterojunction nanozymes.

eg Occupancy as a Predictive Descriptor for Spinel Oxide Nanozymes.

Functional nanomaterials offer an attractive strategy to mimic the catalysis of natural enzymes, which are collectively called nanozymes. Although the development of nanozymes shows a trend of diversification of materials with enzyme-like activity, most nanozymes have been discovered via trial-and-error methods, largely due to the lack of predictive descriptors. To fill this gap, this work identified eg occupancy as an effective descriptor for spinel oxides with peroxidase-like activity and successfully predicted that the eg value of spinel oxide nanozymes with the highest activity is close to 0.6. The LiCo2O4 with the highest activity, which is finally predicted, has achieved more than an order of magnitude improvement in activity. Density functional theory provides a rationale for the reaction path. This work contributes to the rational design of high performance nanozymes by using activity descriptors and provides a methodology to identify other descriptors for nanozymes.

A Noble AuPtAg-GOx Nanozyme for Synergistic Tumor Immunotherapy Induced by Starvation Therapy-Augmented Mild Photothermal Therapy.

Notwithstanding immune checkpoint blocking (ICB) therapy has made eminent clinical breakthroughs, overcoming immunologically "cold" tumors remains challenging. Here, a cascade potentiated nanomodulator AuPtAg-GOx is engineered for boosting immune responsiveness. Upon 1064 nm laser irradiation, AuPtAg-mediated mild photothermal therapy (PTT) activates cytotoxic T lymphocytes and reverses the immunogenic "cold" tumor microenvironment. Further, to amplify the thermal sensitivity of tumor cells, glucose oxidase (GOx) is introduced to suppress the production of heat shock proteins, thereby promoting mild photothermal therapy. Complementarily, AuPtAg nanozymes with catalase-like activity can ameliorate tumor hypoxia, significantly improving the GOx activity. As a result, the combination of AuPtAg-GOx with self-augmented photothermal ability and PD-L1 antibody can further escalate the antitumor efficacy. The AuPtAg-GOx-based synergistic starvation therapy, mild PTT, and immunotherapy cascade enhancement therapy strategy can be a favorable tool to effectively kill cancer cells.

Tensile-Strained Palladium Nanosheets for Synthetic Catalytic Therapy and Phototherapy.

Palladium nanosheets (Pd NSs) are well-investigated photothermal therapy agents, but their catalytic potential for tumor therapy has been underexplored owing to the inactive dominant (111) facets. Herein, lattice tensile strain is introduced by surface reconstruction to activate the inert surface, endowing the strained Pd NSs (SPd NSs) with photodynamic, catalase-like, and peroxidase-like properties. Tensile strain promoting the photodynamic and enzyme-like activities is revealed by density functional theory calculations. Compared with Pd NSs, SPd NSs exhibit lower photothermal effect, but approximately five times higher tumor inhibition rate. This work calls for further study to activate nanomaterials by strain engineering and surface reconstruction for catalytic therapy of tumors.