Platinum Nanozymes Research Articles

Platinum Nanozyme-Loaded Dissolving Microneedles Scavenge ROS and Promote Lineage Progression for Androgenetic Alopecia Treatment.

Androgenetic alopecia (AGA) is a prevalent issue affecting the physical and mental health of individuals but with fewer current treatments. Platinum nanozymes (PtNZs) are known for their excellent ability to reduce and modulate the high oxidative stress environment in AGA pathology. And microneedles are used to overcome the skin barrier due to the poor permeability of PtNZs. Herein, dissolving microneedles loaded with PtNZs (Pt-MNs) are designed and successfully induced hair regeneration in the AGA model. Pt-MNs possessed adequate mechanical strength to breach the skin barrier for effective PtNZs delivery. In vivo, PtNZs first reduced reactive oxygen species (ROS) to oxygen, which recovered the AGA pathological environment. And the oxygen then increased oxidative phosphorylation, promoting the differentiation of hair follicle stem cells to achieve hair regeneration. The group treated with Pt-MNs with a dosing frequency of once every three days achieved faster hair growth than the daily application of the positive drug minoxidil. Further safety experiments showed that the application of Pt-MNs locally opened temporary and recoverable skin channels, with no retention of Pt in major organs, indicating high safety. In conclusion, this study indicated the potential of Pt-MNs as an effective method for treating AGA.

Intra-articular injection of platinum nanozyme-loaded silk fibroin/pullulan hydrogels relieves osteoarthritis through ROS scavenging and ferroptosis suppression

Reactive oxygen species (ROS)-mediated ferroptosis plays a critical role in the development of osteoarthritis (OA). Consequently, it is speculated that anti-ferroptosis agents could represent a novel therapeutic strategy for managing OA. In this study, a hydrogel incorporating platinum (Pt) nanozyme was synthesized by dispersing Pt nanoparticles (NPs) within a matrix of silk fibroin (SF) and oxidized pullulan (oxPL). This hydrogel allows for a substantial and sustained release of up to 30 days. The gelation time (from 140.3 ± 42.3 s to 460.0 ± 40.0 s), swelling capacity (from 57.7 ± 3.8 % to 24.0 ± 7.0 %), and degradation rate (from 60.3 ± 4.7 % to 32.0 ± 4.6 %) of the hydrogels can be modulated by adjusting the Pt NP content. The Pt@SF/oxPL hydrogel effectively eliminates ROS due to its catalase-like and superoxide dismutase-like enzymatic properties. In vitro studies demonstrated that Pt@SF/oxPL efficiently mitigated the process of ferroptotic cell death in chondrocytes. More critically, intra-articular administration of Pt@SF/oxPL showcased therapeutic advantages by both protecting and stimulating the regeneration of cartilage throughout the progression of OA. Collectively, this study suggests that Pt@SF/oxPL hydrogels could potentially serve as an effective treatment for OA, presenting a novel nanozyme-based therapeutic approach for this condition.

Biotemplated Platinum Nanozymes: Synthesis, Catalytic Regulation and Biomedical Applications.

Platinum (Pt) nanozymes with multiple intrinsic enzyme-mimicking activities have attracted extensive attention in biomedical fields due to their high catalytic activity, ease of modification, and convenient storage. However, the Pt nanozymes synthesized by the traditional method often suffer from uncontrollable morphology and poor stability under physicochemical conditions, resulting in unsatisfactory catalytic behavior in practical applications. To optimize the catalytic ability, biological templates have been introduced recently, which can guide the deposition of platinum ions on their surface to form specific morphologies and then stabilize the resulting Pt nanozymes. Given the promising potential of biotemplated Pt nanozymes in practical applications, it is essential to conduct a systematic and comprehensive review to summarize their recent research progress. In this review, we first categorize the biological templates and discuss the mechanisms as well as characteristics of each type of biotemplate in directing the growth of Pt nanozyme. Factors that impact the growth of biotemplated Pt nanozymes are then analyzed, followed by summarizing their biomedical applications. Finally, the challenges and opportunities in this field are outlined. This review article aims to provide theoretical guidance for developing Pt nanozymes with robust functionalities in biomedical applications.

Lab-in-a-Vial Rapid Test for Internet of Things-Embedded Point-of-Healthcare Protein Biomarker Detection in Bodily Fluids.

Amateurs often struggle with detecting and quantifying protein biomarkers in body fluids due to the high expertise required. This study introduces a Lab-in-a-Vial (LV) rapid diagnostic platform, featuring hydrangea-like platinum nanozymes (PtNH), for rapid, accurate detection and quantification of protein biomarkers on-site within 15min. This method significantly enhances detection sensitivity for various biomarkers in body fluids, surpassing traditional methods such as enzyme-linked immunosorbent assays (ELISA) and lateral flow assays (LFA) by ≈250 to 1300 times. The LV platform uses a glass vial coated with specific bioreceptors such as antigens or antibodies, enabling rapid in vitro evaluation of disease risk from small fluid samples, similar to a personal ELISA-like point-of-care test (POCT). It overcomes challenges in on-site biomarker detection, allowing both detection and quantification through a portable wireless spectrometer for healthcare internet of things (H-IoT). The platform's effectiveness and adaptability are confirmed using IgG/IgM antibodies from SARS-CoV-2 infected patients and nuclear matrix protein (NMP22) from urothelial carcinoma (UC) patients as biomarkers. These tests demonstrated its accuracy and flexibility. This approach offers vast potential for diverse disease applications, provided that the relevant protein biomarkers in bodily fluids are identified.

High catalytic nickel−platinum nanozyme enhancing colorimetric detection of Salmonella Typhimurium in milk

Colorimetric qualitative and sensitive quantitative detection of Salmonella Typhimurium (S. Typhimurium) holds significant importance for ensuring food safety and preventing foodborne illnesses. In the study, an ultra-high catalytic activity and biocompatible nickel-platinum nanoparticle (NiPt NP) nanozyme is successful synthesized to prepare a NLISA strategy for the detection of S. Typhimurium. The synthesized NiPt NPs exhibit high oxidase-like catalytic efficiency, with a Michaelis constant (Km) of 0.493 mM, similar to that of natural horseradish peroxidase (HRP). The maximal reaction velocity (Vmax) was determined to be 1.97 × 10-7 M·s-1 exhibiting a 1.97-fold higher than that of the HRP (1.0 × 10-7 M·s-1). Meanwhile, the antibody employed in this NiPt NPs-based NLISA exhibits exceptional capture efficacy, generating a stable immune complex with S. Typhimurium. The NiPt NPs-based NLISA demonstrates sensitivity, specificity, convenience, and cost-efficiency for the detection of S. Typhimurium. Under optimal conditions, this NiPt NPs-based NLISA demonstrates a quantitative range of 103∼106 cfu/mL with a detection limit as low as 103 cfu/mL. A single-blind experimental testing detects different concentrations of S. Typhimurium spiked skim milk, indicating the application potential of the proposed NLISA in real samples. In all, this research provides novel insights into the synthesis of nanozymes with excellent catalytic activity and their applications in S. Typhimurium biosensing.

Multi-Enzyme Cascade Nanoreactors for High-Throughput Immunoassay: Transitioning Concept in Lab to Application in Community.

In this work, we reported a cholesterol oxidase (Chox)-loaded platinum (Pt) nanozyme with the collaborative cascade nanoreactor for the construction of nanozyme-enzyme-linked immunosorbent assay (N-ELSA) models to realize high-throughput rapid evaluation of cancer markers. Considering the high specific surface area and manipulable surface sites, ZIF-8 was used as a substrate for natural enzyme and nanozyme loading. The constructed ZIF-8-Pt nanozyme platform exhibited efficient enzyme-like catalytic efficiency with a standard corrected activity of 60.59 U mg-1, which was 12 times higher than that of the ZIF-8 precursor, and highly efficient photothermal conversion efficiency (∼35.49%). In N-ELISA testing, developed multienzyme photothermal probes were immobilized in microplates based on antigen-antibody-specific reactions. Cholesterol was reacted in a cascade to reactive oxygen radicals, which attacked 3,3',5,5'-tetramethylbenzidine, causing it to oxidize and color change, thus exhibiting highly enhanced efficient photothermal properties. Systematic temperature evaluations were performed by a hand-held microelectromechanical system thermal imager under the excitation of an 808 nm surface light source to determine the cancer antigen 15-3 (CA15-3) profiles in the samples. Encouragingly, the temperature signal from the microwells increased with increasing CA15-3, with a linear range of 2 mU mL-1 to 100 U mL-1, considering it to be the sensor with the widest working range for visualization and portability available. This work provides new horizons for the development of efficient multienzyme portable colorimetric-photothermal platforms to help advance the community-based process of early cancer detection.

Choline Phosphate-Grafted Nanozymes as Universal Extracellular Vesicle Probes for Bladder Cancer Detection.

Urinary extracellular vesicles (uEVs) are regarded as highly promising liquid-biopsy biomarkers for the early diagnosis and prognosis of bladder cancer (BC). However, detection of uEVs remains technically challenging owing to their huge heterogeneity and ultralow abundance in real samples. We herein present a choline phosphate-grafted platinum nanozyme (Pt@CP) that acts as a universal EV probe for the construction of a high-throughput and high-sensitivity immunoassay, which allowed multiplex profiling of uEV protein markers for BC detection. With the Pt@CP-based immunoassays, three uEV protein markers (MUC-1, CCDC25, and GLUT1) were identified for BC, by which the BC cases (n = 48), cystitis patients (n = 27), and healthy donors (n = 24) were discriminated with high clinical sensitivity and specificity (area under curve = 98.3%). For the BC cases (n = 9) after surgery, the Pt@CP-based immunoassay could report the postoperative residual tumor that cannot be observed by cystoscopy, which is clinically significant for assessing BC recurrence. This work provides generally high sensitivity for EV detection, facilitating the discovery and clinical use of EV-based biomarkers.

Platinum Nanozyme Probes for Cellular Imaging by Electron Microscopy

The highly efficient peroxidase‐like activity of platinum nanozymes (3–20 nm size) is exploited within the complex cellular environment to catalyze the oxidation of the DAB substrate, producing an electron‐dense signal around the nanozyme surface, upon osmium staining. It is proved that such nanozyme amplification can achieve a catalytic signal enhancement up to 10‐fold, enabling the quick detection of the Pt particles (even of 3 nm size) by transmission electron microscopy (TEM) also at low magnification and across wide fields of view in the intricate intracellular milieu. The developed procedure is ideally suited to overcome standard amplification strategies currently used in TEM analysis, such as gold or silver enhancements. Furthermore, the wide versatility of the Pt‐nanozyme probes in TEM imaging is demonstrated in immuno‐EM and protein trafficking studies, showing their potential to track the subcellular localization of target biomolecules at both low and high magnifications. These results suggest that the use of nanozymes might represent a paradigm shift in the conventional amplification systems currently employed in electron microscopy for cellular analyses, offering enhanced imaging capabilities.

Metrology of Platinum Nanozymes: Mechanistic Insights and Analytical Issues (Adv. Funct. Mater. 24/2024)

Metrology of Platinum Nanozymes: Mechanistic Insights and Analytical Issues (Adv. Funct. Mater. 24/2024)

A nano-oxygen generator for enhanced light-controlled elimination of anaerobic bacteria in periodontal infections

Using nanomaterials with photodynamic therapy (PDT) to combat bacterial infections including periodontal infections has attracted the attention of researchers because of their high efficiency, simplicity and low susceptibility to drug resistance. However, the therapeutic effectiveness is threatened by the endogenous accumulation of hydrogen peroxide and insufficient amounts of the substrate oxygen. Here, we report a microporous Zr porphyrin carboxylate metal-organic framework (MOF) PCN-222 doped with platinum nanozymes, Pt@PCN-222, to reshape the microenvironment that is not conducive to the recovery of infected tissue and further promote recovery after periodontal tissue infection. This MOFdoped with platinum nanozymes can remove excessive endogenous hydrogen peroxide and produce dissolved oxygen simultaneously. This framework can effectively alleviate anaerobic bacterial infection in periodontal tissue, including efficiently killing the bacteria and reducing the level of inflammation in tissue. This work provides a new strategy to solve the long-term clinical challenge of anaerobic bacterial infections in periodontal tissue and proposes an innovative approach to improve treatment.

Biomimetic Integrated Nanozyme for Flare and Recurrence of Gouty Arthritis

Flare and multiple recurrences pose significant challenges in gouty arthritis. Traditional treatments provide temporary relief from inflammation but fail to promptly alleviate patient pain or effectively prevent subsequent recurrences. It should also be noted that both anti-inflammation and metabolism of uric acid are necessary for gouty arthritis, calling for therapeutic systems to achieve these two goals simultaneously. In this study, we propose a biomimetic integrated nanozyme, HMPB-Pt@MM, comprising platinum nanozyme and hollow Prussian blue. It demonstrates anti-inflammatory properties by eliminating reactive oxygen species and reducing infiltration of inflammatory macrophages. Additionally, it rapidly targets inflamed ankles through the camouflage of macrophage membranes. Furthermore, HMPB-Pt@MM exhibits urate oxidase-like capabilities, continuously metabolizing locally elevated uric acid concentrations, ultimately inhibiting multiple recurrences of gouty arthritis. In summary, HMPB-Pt@MM integrates ROS clearance with uric acid metabolism, offering a promising platform for the treatment of gouty arthritis.

Platinum nanozyme co-loaded reactive oxygen species-responsive prodrug integrated with dissolvable microneedle for chemotherapy and photodynamic therapy of melanoma

Melanoma, the most aggressive form of skin cancer, is characterized by an increasing incidence rate. However, conventional treatment methods such as surgery, chemotherapy, radiotherapy, and immunotherapy have limitations that hinder their widespread application. In this study, we aim to develop a platinum nanozyme (PtNP) co-loaded reactive oxygen species (ROS)-responsive prodrug integrated with dissolvable microneedle for chemotherapy and photodynamic therapy of melanoma. The utilization of microneedle can significantly enhance the efficiency of transdermal drug delivery while improving treatment efficacy and minimizing toxic side effects. The nanodrug system incorporates a prodrug composed of chemotherapeutic agent, photosensitizer, and ROS-responsive chemical bond. Upon laser irradiation, it generates ROS for effective photodynamic therapy while precisely controlling the release behavior of camptothecin (CPT) within the prodrug formulation. Furthermore, PtNP in the nanodrug exhibits nanozyme-like activity by catalyzing the decomposition of hydrogen peroxide into oxygen to overcome hypoxia-related challenges and enhance the effectiveness of photodynamic therapy. The integration of the nanodrug complex with dissolvable microneedle presents a synergistic approach for the combined delivery of chemotherapy and photodynamic therapy to melanoma patients, offering novel strategies and avenues for clinical treatment.

Metrology of Platinum Nanozymes: Mechanistic Insights and Analytical Issues

AbstractThanks to their properties, stability, and multifunctionality, nanozymes are increasingly impacting several fields, including medicine, diagnostics, and environmental science. However, clear information about their catalytic properties and mechanisms is still lacking. Several critical issues are currently under discussions, such as the absence of univocally accepted catalytic mechanisms, standardized protocols for directly comparing nanozymes versus enzymes, and a comprehensive characterization of their performance in different chemical/biological environments. All these issues strongly limit the advancement of the field. Herein, nanozymes metrology and analysis of both catalytic mechanisms and methodological procedures are attempted, taking platinum nanozymes as a case study thanks to their multifunctional catalytic features. The oxidoreductase activities of Pt‐nanozymes (i.e., peroxidase‐, oxidase‐, and catalase‐like reactions) are critically investigated in different physical/chemical environments, clarifying fundamental aspects and providing general methodological guidelines for nanozyme properties characterization. Furthermore, PtNP activities are compared with natural enzymes in different conditions, and their performance and catalytic behavior are evaluated by calculating the turnover frequency (TOF) with different normalization strategies. The results highlight that Pt‐nanozymes are efficient catalysts, exhibiting outstanding catalase‐like activity. This work clarifies several key points concerning Pt‐nanozyme properties and general metrological issues, providing a workflow that can become a reference for several nanozymes characterizations.

Oxygen-supplying ROS-responsive prodrug for synergistic chemotherapy and photodynamic therapy of colon cancer.

Introduction: The synergistic treatment of chemotherapy and photodynamic therapy (PDT) has remarkable potential in cancer therapy. However, challenges remain, such as unstable chemotherapeutic drug release, suboptimal targeting, and reduced efficacy of PDT under hypoxic conditions commonly found in solid tumors. Methods: To address these issues, we use camptothecin (CPT) and pheophorbide a (Pa) incorporated through the functional thioketal, which serves as the reactive oxygen species (ROS)-responsive trigger, to construct a ROS-responsive prodrug (CPT-TK-Pa). Subsequently, we co-loaded it with a platinum nanozyme (PtNP) in distearylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) to obtain the ROS-responsive prodrug nanoparticle (CPT-TK-Pa/Pt NP). Results and Discussion: Specifically, the incorporated PtNP within CPT-TK-Pa/Pt NP positively catalyzes the conversion of hydrogen peroxide (H2O2) to oxygen, thereby ameliorating the hypoxic state of the tumor. This enhanced oxygen generation could replenish the oxygen that is consumed by Pa during 660nm exposure, enabling controlled CPT release and amplifying the photodynamic response. In vitro investigations reveal the potency of CPT-TK-Pa/Pt NPs in inhibiting colon tumor cells. Given its ROS-responsive release mechanism and enhanced PDT efficacy, CPT-TK-Pa/Pt NP has the potential to be a promising candidate for cancer therapy.

Surface ligand-regulated nanointerfaces: Enhancing the catalytic activity and selectivity of platinum nanozymes for biomedical applications

Platinum nanoparticles (Pt NPs) have aroused tremendous attention due to the significant enzyme-like activity, controllable synthesis and biosafety. However, it remains a challenge to properly design the morphology and surface properties of Pt NPs to obtain the desired enzyme-like activity and substrate selectivity. Herein, a surface engineering strategy is employed to adjust the catalytic performance of Pt NPs by modifying different functional groups, thereby promoting its oxidase-like activity and catalytic specificity to substrate. The catalytic performance of Pt NPs with various thiolate ligands was evaluated using TMB, ABTS and OPD as substrates. The kcat/Km values revealed that Pt NPs modified by 6-mercapto-6-deoxybeta-cyclodextrin (Pt@CD) had a strong substrate selectivity for TMB, but a weak selectivity for ABTS and OPD, with a catalytic specificity to TMB nearly 3.4 times that of bare Pt NPs. When uric acid was used as substrate, PtNP_32 showed better environmental stability and uric acid degradation efficiency than uricase. More importantly, the PtNP_32 did not cause hemolysis and had good biocompatibility, making it a promising candidate for the treatment of hyperuricemia-related diseases. This work provides a new strategy to improve the catalytic performance of platinum nanozymes for efficient and selective degradation of uric acid.

Near-infrared light-heatable platinum nanozyme for synergistic bacterial inhibition.

The development of non-antibiotic strategies for bacterial disinfection is of great clinical importance. Among recently developed different antimicrobial strategies, nanomaterial-mediated approaches, especially the photothermal way and reactive oxygen species (ROS)-generating method, show many significant advantages. Although promising, the clinical application of nanomaterials is still limited, owing to the potential biosafety issues. Further improvement of the antimicrobial activity to reduce the usage, and thus reduce the potential risk, is an important way to increase the clinical applicability of antibacterial nanomaterials. In this paper, an antimicrobial nanostructure with both an excellent photothermal effect and peroxidase-like activity was constructed to achieve efficient synergistic antimicrobial activity. The obtained nano-antimicrobial agent (ZIF-8@PDA@Pt) can not only efficiently catalyze the production of ROS from H2O2 to cause damage to bacteria but also convert the photon energy of near-infrared light into thermal energy to kill bacteria, and the two synergistic effects induced in a highly efficient antimicrobial activity. This study not only offers a new nanomaterial with efficient antibacterial activity but also proposes a new idea for constructing synergistic antibacterial properties.

Nanozymes in Alzheimer's disease diagnostics and therapy.

Alzheimer's disease (AD) is a progressive neurodegenerative condition that has become an important public health problem of global concern, and the early diagnosis and etiological treatment of AD are currently the focus of research. In the course of clinical treatment, approved clinical drugs mainly serve to slow down the disease process by relieving patients' clinical symptoms. However, these drugs do not target the cause of the disease, and the lack of specificity of these drugs has led to undesirable side effects in treatment. Meanwhile, AD is mainly diagnosed by clinical symptoms and imaging, which does not have the advantage of early diagnosis. Nanozymes have been extensively investigated for the diagnosis and treatment of AD with high stability and specificity. Therefore, this review summarizes the recent advances in various nanozymes for AD diagnosis and therapy, including with peroxidase-like-activity gold nanozymes, iron nanozymes, superoxide dismutase-like- and catalase-like-activity selenium dioxide nanozymes, platinum nanozymes, and peroxidase-like palladium nanozymes, among others. A comprehensive analysis was conducted on the diagnostic and therapeutic characteristics of nanozyme therapy for AD, as well as the prospects and challenges of its clinical application. Our goal is to advance this emerging topic by building on our own work and the new insights we have learned from others. This review will assist researchers to quickly understand relevant nanozymes' therapeutic and diagnostic information and further advance the field of nanozymes in AD.

Carbon dot enhanced peroxidase-like activity of platinum nanozymes.

As one of the most intriguing nanozymes, the platinum (Pt) nanozyme has attracted tremendous research interest due to its various catalytic activities but its application is still limited by its poor colloidal stability and low affinity to substrates. Here, we design a highly stable Pt@carbon dot (Pt@CD) hybrid nanozyme with enhanced peroxidase (POD)-like activity (specific activity of 1877 U mg-1). The Pt@CDs catalyze the decomposition of hydrogen peroxide (H2O2) to produce singlet oxygen and hydroxyl radicals and exhibit high affinity to H2O2 and high specificity to 3,3',5,5'-tetramethyl-benzidine. We reveal that both the hydroxyl and carbonyl groups of CDs could coordinate with Pt2+ and then regulate the charge state of the Pt nanozyme, facilitating the formation of Pt@CDs and improving the POD-like activity of Pt@CDs. Colorimetric detection assays based on Pt@CDs for H2O2, dopamine, and glucose with a satisfactory detection performance are achieved. Moreover, the Pt@CDs show a H2O2-involving antibacterial effect by destroying the cell membrane. Our findings provide new opportunities for designing hybrid nanozymes with desirable stability and catalytic performance by using CDs as nucleating templates and stabilizers.

A bimetallic nanozyme coordinated with quercetin for efficient radical scavenging and treatment of acute kidney injury.

Acute kidney injury (AKI), characterized by tissue inflammation and oxidative damage, is a common and potentially life-threatening complication in patients. Quercetin, a natural antioxidant, possesses diverse pharmacological properties. However, limited stability and bioavailability hinder its clinical utilization. Moreover, the application of nanotechnology in antioxidant strategies for AKI treatment faces significant knowledge gaps. These gaps stem from limited understanding of the therapeutic mechanisms and renal clearance pathways. To tackle these issues, this study aims to develop an anti-oxidation nanozyme through the coordination of quercetin (Que) with a ruthenium (Ru) doped platinum (Pt) nanozyme (RuPt nanozyme). Compared to using Que or the RuPt nanozyme alone, the combined use of Que and the nanozyme led to enhanced antioxidant activities, especially in ABTS and DPPH free radical scavenging activities. Moreover, the modified nanozyme showed remarkable efficacy in scavenging reactive oxygen species and inhibiting apoptosis in a H2O2-induced cellular model. Additionally, the in vivo study showed that the coordination-modified nanozyme effectively alleviated glycerol- and cisplatin-induced AKI by inhibiting oxidative stress. Furthermore, this nanozyme exhibited superior therapeutic efficacy when compared to free quercetin and the RuPt nanozyme. In conclusion, the findings of our study suggest that the quercetin modified RuPt nanozyme (QCN) exhibits remarkable biocompatibility and holds significant promise for the therapeutic management of AKI.

Single-step colorimetric detection of acid phosphatase in human urine using an oxidase-mimic platinum nanozyme

A nanozyme sensor for rapid detection of urinary acid phosphatase with high sensitivity and a broad dynamic range that is relevant to human pathophysiology is proposed.