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Natural enzymes are efficient and versatile biocatalysts but suffer in their environmental tolerance and catalytic stability. As artificial enzymes, nanozymes can improve the catalytic stability, but it is still a challenge to achieve high catalytic activity. Here, we employed atomic engineering to build the artificial enzyme named Au24Ag1 clusterzyme that hosts an ultrahigh catalytic activity as well as strong physiological stability via atom manipulation. The designed Au24Ag1 clusterzyme activates the Ag-S active site via lattice expansion in the oligomer atom layer, showing an antioxidant property 72 times higher than that of natural antioxidant Trolox. Enzyme-mimicked studies find that Au24Ag1 clusterzyme exhibits high catalase-like (CAT-like) and glutathione peroxidase-like (GPx-like) activity with a maximum reaction rate of 68.9 and 17.8 µM/min, respectively. Meanwhile, the unique catalytic landscape exhibits distinctive reactions against inflammation by inhibiting the cytokines at an early stage in the brain. Atomic engineering of clusterzymes provides a powerful and attractive platform with satisfactory atomic dispersion for tailoring biocatalysts freely at the atomic level.
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Catálise , Catalase/genéticaRESUMO
Radiotherapy has been widely used in clinical cancer treatment. However, the ionizing radiation required to kill the tumor will inevitably cause damage to the surrounding normal tissues. To minimize the radiation damage and side effects, small molecular radioprotective agents have been used as clinical adjuvants for radiation protection of healthy tissues. However, the shortcomings of small molecules such as short circulation time and rapid kidney clearance from the body greatly hinder their biomedical applications. In recent years, nanozymes have attracted much attention because of their potential to treat a variety of diseases. Nanozymes exhibit catalytic properties and antioxidant capabilities to provide a potential solution for the development of high-efficiency radioprotective agents in radiotherapy and nuclear radiation accidents. Therefore, in this review, we systematically summarize the catalytic nanozymes used for radiation protection of healthy tissues and discuss the challenges and future prospects of nanomaterials in the field of radiation protection.
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Enzimas/química , Nanoestruturas , Proteção Radiológica , Animais , Carbono/química , Catálise , Grafite/química , Metais/química , Óxidos/química , Pontos Quânticos , Sulfetos/químicaRESUMO
The artificial enzymes at the atomic level have shown great potential in chemical biology and nanomedicine, and modulation of catalytic selectivity is also critical to the application of nanozymes. In this work, atomic precision Ag25 clusterzymes protected by single- and dual-ligand were developed. Further, the catalytic activity and selectivity of Ag25 clusterzymes were modulated by adjusting doping elements and ligand. The Ag24Pt1 shows more prominent antioxidant activity characteristics in the dual-ligand system, while the Ag24Cu1 possesses the superoxide dismutase-like (SOD-like) activity regardless of the single- or dual-ligand system, indicating modulated catalytic selectivity. In vitro experiments showed the Ag24Pt1-D can recover radiation induced DNA damages and eliminate the excessive reactive oxygen species (ROS) generated from radiation. Subsequent in vivo radiation protection experiments reveal that Ag24Cu1-S and Ag24Pt1-D can improve the survival rate of irradiated mice from 0 to 40% and 30%, respectively. The detailed biological experiments confirm that the Ag24Cu1-S and Ag24Pt1-D can recover the SOD and 3,4-methylenedioxyamphetamine (MDA) levels via suppressing the chronic inflammation reaction. Nearly 60% of Ag24Cu1-S and Ag24Pt1-D can be excreted after a 1 day injection, and no obvious toxicological reactions were observed 30 days after injection.
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Superóxido DismutaseRESUMO
BACKGROUND: Neurotrauma is a worldwide public health problem which can be divided into primary and secondary damge. The primary damge is caused by external forces and triggers the overproduction of peroxides and superoxides, leading to long-lasting secondary damage including oxidative stress, wound infection and immunological reactions. The emerging catalysts have shown great potential in the treatment of brain injury and neurogenic inflammation, but are limited to biosafety issues and delivery efficiency. RESULTS: Herein, we proposed the noninvasive delivery route to brain trauma by employing highly active gold clusters with enzyme-like activity to achieve the early intervention. The decomposition rate to H2O2 of the ultrasmall gold clusters is 10 times that of glassy carbon (GC) electrodes, indicating excellent catalytic activity. The gold clusters can relieve the oxidative stress and decrease the excessive O2·- and H2O2 both in vitro and in vivo. Besides, gold clusters can accelerate the wound healing of brain trauma and alleviate inflammation via inhibiting the activation of astrocytes and microglia through noninvasive adminstration. decrease the peroxide and superoxide of brain tissue. CONCLUSIONS: Present work shows noninvasive treatment is a promising route for early intervention of brain trauma.
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Antioxidantes , Ouro , Nanopartículas Metálicas , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Catálise , Modelos Animais de Doenças , Ouro/química , Ouro/farmacologia , Peróxido de Hidrogênio/metabolismo , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Camundongos , Camundongos Endogâmicos C57BL , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacosRESUMO
Reactive oxygen and nitrogen species (RONS), especially reactive nitrogen species (RNS) are intermediate products during incidence of nervous system diseases, showing continuous damage for traumatic brain injury (TBI). Here, we developed a carbogenic nanozyme, which shows an antioxidant activity 12 times higher than ascorbic acid (AA) and behaves as multienzyme mimetics. Importantly, the nanozyme exhibits an ultrahigh scavenging efficiency (â¼16 times higher than AA) toward highly active RNS, such as â¢NO and ONOO- as well as traditional reactive oxygen species (ROS) including O2â¢-, H2O2, and â¢OH. In vitro experiments show that neuron cells injured by H2O2 or lipopolysaccharide can be significantly recovered after carbogenic nanozyme treatment via scavenging all kinds of RONS. Moreover, the carbogenic nanozyme can serve as various enzyme mimetics and eliminate the harmful peroxide and glutathione disulfide from injured mice, demonstrating its potential as a therapeutic for acute TBI.
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Materiais Biomiméticos , Lesões Encefálicas Traumáticas , Dissulfeto de Glutationa/metabolismo , Peróxido de Hidrogênio/metabolismo , Nanoestruturas , Espécies Reativas de Nitrogênio/metabolismo , Doença Aguda , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Lesões Encefálicas Traumáticas/tratamento farmacológico , Lesões Encefálicas Traumáticas/metabolismo , Lesões Encefálicas Traumáticas/patologia , Modelos Animais de Doenças , Camundongos , Nanoestruturas/química , Nanoestruturas/uso terapêuticoRESUMO
Catalytic nanomaterials can be used extrinsically to combat diseases associated with a surplus of reactive oxygen species (ROS). Rational design of surface morphologies and appropriate doping can substantially improve the catalytic performances. In this work, a class of hollow polyvinyl pyrrolidone-protected PtPdRh nanocubes with enhanced catalytic activities for in vivo free radical scavenging is proposed. Compared with Pt and PtPd counterparts, ternary PtPdRh nanocubes show remarkable catalytic properties of decomposing H2 O2 via enhanced oxygen reduction reactions. Density functional theory calculation indicates that the bond of superoxide anions breaks for the energetically favorable status of oxygen atoms on the surface of PtPdRh. Viability of cells and survival rate of animal models under exposure of high-energy γ radiation are considerably enhanced by 94% and 50% respectively after treatment of PtPdRh nanocubes. The mechanistic investigations on superoxide dismutase (SOD) activity, malondialdehyde amount, and DNA damage repair demonstrate that hollow PtPdRh nanocubes act as catalase, peroxidase, and SOD analogs to efficiently scavenge ROS.
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Nanoestruturas/química , Paládio/química , Platina/química , Espécies Reativas de Oxigênio/metabolismo , Catalase/metabolismo , Catálise , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Peroxidase/metabolismo , Superóxido Dismutase/metabolismoRESUMO
A rapid and highly selective naked-eye detection of hydrochloric acid (HCl) in an aqueous medium was established using HCl-triggered redispersion of gold nanoparticle aggregates.
RESUMO
An AND logic gate-based Hg2+ ion colorimetric assay was constructed using the plasmonic and nanozyme dual signal channels of gold nanoparticles (AuNPs). This assay increased the judgment criteria for the identification of Hg2+ ions and effectively improved the accuracy of Hg2+ ion detection.
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Implanted neural electrodes have been widely used to treat brain diseases that require high sensitivity and biocompatibility at the tissue-electrode interface. However, currently used clinical electrodes cannot meet both these requirements simultaneously, which hinders the effective recording of electronic signals. Herein, nanozyme-based neural electrodes incorporating bioinspired atomically precise clusters are developed as a general strategy with a heterogeneous design for multiscale and ultrasensitive neural recording via quantum transport and biocatalytic processes. Owing to the dual high-speed electronic and ionic currents at the electrode-tissue interface, the impedance of nanozyme electrodes is 26 times lower than that of state-of-the-art metal electrodes, and the acquisition sensitivity for the local field potential is ≈10 times higher than that of clinical PtIr electrodes, enabling a signal-to-noise ratio (SNR) of up to 14.7 dB for single-neuron recordings in rats. The electrodes provide more than 100-fold higher antioxidant and multi-enzyme-like activities, which effectively decrease 67% of the neuronal injury area by inhibiting glial proliferation and allowing sensitive and stable neural recording. Moreover, nanozyme electrodes can considerably improve the SNR of seizures in acute epileptic rats and are expected to achieve precise localization of seizure foci in clinical settings.
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Neurônios , Ratos , Animais , Eletrodos , Eletrodos Implantados , Razão Sinal-Ruído , Neurônios/fisiologia , Impedância Elétrica , MicroeletrodosRESUMO
Strong fluorescence and high catalytic activities cannot be achieved simultaneously due to conflicts in free electron utilization, resulting in a lack of bioactivity of most near-infrared-II (NIR-II) fluorophores. To circumvent this challenge, we developed atomically precise Au22 clusters with strong NIR-II fluorescence ranging from 950 to 1300 nm exhibiting potent enzyme-mimetic activities through atomic engineering to create active Cu single-atom sites. The developed Au21Cu1 clusters show 18-fold higher antioxidant, 90-fold higher catalase-like, and 3-fold higher superoxide dismutase-like activities than Au22 clusters, with negligible fluorescence loss. Doping with single Cu atoms decreases the bandgap from 1.33 to 1.28 eV by predominant contributions from Cu d states, and Cu with lost electron states effectuates high catalytic activities. The renal clearable clusters can monitor cisplatin-induced renal injury in the 20- to 120-minute window and visualize it in three dimensions using NIR-II light-sheet microscopy. Furthermore, the clusters inhibit oxidative stress and inflammation in the cisplatin-treated mouse model, particularly in the kidneys and brain.
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Ouro , Imageamento Tridimensional , Animais , Camundongos , Cisplatino , Corantes Fluorescentes , Microscopia de Fluorescência , Imagem Óptica/métodosRESUMO
Traumatic brain injury (TBI) is a sudden injury to the brain, accompanied by the production of large amounts of reactive oxygen and nitrogen species (RONS) and acute neuroinflammation responses. Although traditional pharmacotherapy can effectively decrease the immune response of neuron cells via scavenging free radicals, it always involves in short reaction time as well as rigorous clinical trial. Therefore, a noninvasive topical treatment method that effectively eliminates free radicals still needs further investigation. Methods: In this study, a type of catalytic patch based on nanozymes with the excellent multienzyme-like activity is designed for noninvasive treatment of TBI. The enzyme-like activity, free radical scavenging ability and therapeutic efficacy of the designed catalytic patch were assessed in vitro and in vivo. The structural composition was characterized by the X-ray diffraction, X-ray photoelectron spectroscopy and high-resolution transmission electron microscopy technology. Results: Herein, the prepared Cr-doped CeO2 (Cr/CeO2) nanozyme increases the reduced Ce3+ states, resulting in its enzyme-like activity 3-5 times higher than undoped CeO2. Furthermore, Cr/CeO2 nanozyme can improve the survival rate of LPS induced neuron cells via decreasing excessive RONS. The in vivo experiments show the Cr/CeO2 nanozyme can promote wound healing and reduce neuroinflammation of mice following brain trauma. The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases. Conclusions: The catalytic patch based on nanozyme provides a noninvasive topical treatment route for TBI as well as other traumas diseases.
Assuntos
Lesões Encefálicas Traumáticas/tratamento farmacológico , Catálise/efeitos dos fármacos , Cério/administração & dosagem , Compostos de Cromo/administração & dosagem , Oxirredução/efeitos dos fármacos , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Lesões Encefálicas Traumáticas/metabolismo , Linhagem Celular , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Taxa de Sobrevida , Cicatrização/efeitos dos fármacosRESUMO
Emerging artificial enzymes with reprogrammed and augmented catalytic activity and substrate selectivity have long been pursued with sustained efforts. The majority of current candidates have rather poor catalytic activity compared with natural molecules. To tackle this limitation, we design artificial enzymes based on a structurally well-defined Au25 cluster, namely clusterzymes, which are endowed with intrinsic high catalytic activity and selectivity driven by single-atom substitutions with modulated bond lengths. Au24Cu1 and Au24Cd1 clusterzymes exhibit 137 and 160 times higher antioxidant capacities than natural trolox, respectively. Meanwhile, the clusterzymes demonstrate preferential enzyme-mimicking catalytic activities, with Au25, Au24Cu1 and Au24Cd1 displaying compelling selectivity in glutathione peroxidase-like (GPx-like), catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) activities, respectively. Au24Cu1 decreases peroxide in injured brain via catalytic reactions, while Au24Cd1 preferentially uses superoxide and nitrogenous signal molecules as substrates, and significantly decreases inflammation factors, indicative of an important role in mitigating neuroinflammation.
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Enzimas/química , Inflamação , Neurônios/enzimologia , Compostos Organometálicos/química , Animais , Antioxidantes , Encéfalo/enzimologia , Catalase , Catálise , Linhagem Celular , Glutationa Peroxidase/química , Masculino , Metais/química , Camundongos Endogâmicos C57BL , Modelos Moleculares , Neurônios/imunologia , Superóxido Dismutase/química , SuperóxidosRESUMO
Artificial enzymes have attracted wide interest in disease diagnosis and biotechnology due to high stability, easy synthesis, and cost effectiveness. Unfortunately, their catalytic rate is limited to surface electron transfer, affecting the catalytic and biological activity. Here, we report an oligomeric nanozyme (O-NZ) with ultrafast electron transfer, achieving ultrahigh catalytic activity. O-NZ shows electron transfer of 1.8 nanoseconds in internal cores and 1.2 picoseconds between core and ligand molecule, leading to ultrahigh superoxidase dismutaselike and glutathione peroxidaselike activity (comparable with natural enzyme, Michaelis constant = 0.87 millimolars). Excitingly, O-NZ can improve the 1-month survival rate of mice with acute brain trauma from 50 to 90% and promote the recovery of long-term neurocognition. Biochemical experiments show that O-NZ can decrease harmful peroxide and superoxide via in vivo catalytic chain reaction and reduce acute neuroinflammation via nuclear factor erythroid-2 related factor 2mediated up-regulation of heme oxygenase-1 expression.
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In recent years, the rapid development of nanoscience and technology has provided a new opportunity for the development and preparation of new inorganic enzymes. Nanozyme is a new generation of artificial mimetic enzyme, which like natural enzymes, can efficiently catalyze the substrate of enzyme under mild conditions, exhibiting catalytic efficiency, and enzymatic reaction kinetics similar to natural enzymes. However, nanozymes exist better stability than native enzymes, it can still maintain 85 % catalytic activity in strong acid and alkali (pH 2~10) or large temperature range (4~90°C). This provides conditions for designing complex catalytic systems. In this review, we discussed the enzymatic attributes and biomedical applications of gold nanoclusters, including peroxidase-like, catalase-like, detection of heavy metal ions, and therapy of brain and cancer etc. This review can help us understand the current research status nanozymes.
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Hypoxia is known to be a common feature within many types of solid tumors, which is closely related to the limited efficacy of radiotherapy. Meanwhile, due to the non-discriminatory killing effect of both normal and cancer cells during the radiation process, traditional radiosensitizers could bring severe non-negligible side-effects to the whole body. In this work, stable and atomically precise Mn clusters which possess efficient pH-triggered catalytic selective capacity are developed rationally. Mn clusters could efficiently catalyze oxygen production in an acidic tumor microenvironment, while exhibiting strong reducibility and free radical scavenging ability in neutral circumstances. In vivo experiments show that Mn clusters are able to enhance the radiotherapy effect in the mouse model of 4T1 tumors and protect normal tissues from radiation at the same time. Thus, the present work provides a novel dual-functional strategy to enhance radiotherapy-induced tumor treatment by improving tumor oxygenation and protect normal tissues from radiation simultaneously.
Assuntos
Manganês , Neoplasias/radioterapia , Protetores contra Radiação/uso terapêutico , Radiossensibilizantes/uso terapêutico , Animais , Células CHO , Catálise , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos da radiação , Cricetulus , Concentração de Íons de Hidrogênio , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Camundongos , Oxirredução , Protetores contra Radiação/síntese química , Protetores contra Radiação/química , Radiossensibilizantes/síntese química , Radiossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Resultado do Tratamento , Microambiente TumoralRESUMO
Atomically precise Au25(SG)18 clusters have shown great promise in near-infrared II cerebrovascular imaging, X-ray imaging, and cancer radiotherapy due to their high atomic number, unique molecular-like electronic structure, and renal clearable properties. Therefore, it is important to study the in vivo toxicity of Au25 clusters. Unfortunately, previous toxicological investigations focused on low injected doses (<100 mg kg-1) and routine research methods, such as blood chemistry and biochemistry, which cannot reflect neurotoxicity or tiny changes in neural activity. In this work, in vivo neuroelectrophysiology of Au25 clusters at ultrahigh injected doses (200, 300, and 500 mg kg-1) was investigated. Local field potential showed that the Au25-treated mice showed a spike in delta rhythm and moved to lower frequency over time. The power spectrum showed a 38.3% reduction in the peak value at 10 h post-injection of Au25 clusters compared with 3 h post-injection, which gradually became close to the normal level, indicating no permanent damage to the nervous system. Moreover, no significant structural changes were found in both neurons and glial cells at the histological level. These results of in vivo neuroelectrophysiology will encourage scientists to make more exciting discoveries on nervous system diseases by employing Au25 clusters even at ultrahigh injected doses.
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Killing tumor cells with a visualized system is a promising strategy in tumor therapy to achieve minimal side effects and high efficiency. Herein, a theranostic nanomedicine (AuNCs-Pt) is developed based on nanocarrier gold nanoclusters (AuNCs) with bifunctions of both NIR-I/NIR-II imaging and glutathione-scavenging abilities. AuNCs-Pt possesses NIR-II imaging capability on a fatal high-grade serous ovarian cancer (HGSOC) model in the deep abdomen, thus facilitating it to be a promising tool for monitoring platinum transportation. Meanwhile, AuNCs-Pt depletes intracellular glutathione to minimize platinum detoxification, effectively maximizing the chemotherapeutic efficacy of platinum. AuNCs-Pt is used to eradicate the tumor burden in this study on a HGSOC model and a patient-derived tumor xenograft model of hepatocellular carcinoma, suggesting great potential for clinical visualized therapy and platinum drug sensitization.
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Neoplasias Hepáticas , Nanopartículas Metálicas , Glutationa , Ouro , Humanos , Platina , Nanomedicina TeranósticaRESUMO
Free radical-induced oxidative damage and nitrosative stress have been identified as key factors in neuroinflammation responses after traumatic brain injury (TBI), with which reactive oxygen and nitrogen species (RONS), especially nitrogen signaling molecules, are strongly associated. Here, we prepared ultrasmall carbon dot (CD) by using a simple and facile method. In vitro assessment experiments show that the antioxidative CD exhibits an ultrahigh target-scavenging effect for nitrogen signaling molecules, especially the highly reactive ËNO and ONOO-. However, CD can only partially eliminate conventional oxygen radials such as O2Ë- and ËOH, indicating CD has a preference for RNS modulation. Moreover, in vitro cell experiments and in vivo mice experiments reveal that CD can reduce the reactive oxygen species (ROS) level and lipid peroxidation, enhance superoxide dismutase (SOD) activity and GSSG level, and further improve the survival rate of neuron cells and TBI mice. These results declare that antioxidative CD could serve as an effective therapeutic for TBI.
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Antioxidantes/química , Lesões Encefálicas Traumáticas/tratamento farmacológico , Carbono/química , Pontos Quânticos/química , Espécies Reativas de Nitrogênio/química , Animais , Antioxidantes/farmacologia , Transporte Biológico , Barreira Hematoencefálica/metabolismo , Morte Celular/efeitos dos fármacos , Cisteína/química , Modelos Animais de Doenças , Radicais Livres/química , Radicais Livres/metabolismo , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Lisina/química , Camundongos , Camundongos Endogâmicos C57BL , Teste do Labirinto Aquático de Morris/efeitos dos fármacos , Neurônios/citologia , Estresse Oxidativo/efeitos dos fármacos , Pontos Quânticos/metabolismo , Espécies Reativas de Nitrogênio/metabolismo , Espécies Reativas de Oxigênio/química , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Distribuição TecidualRESUMO
Pharmaceutical evaluations of nanomedicines are of great significance for their further launch into industry and clinic. Near-infrared (NIR) fluorescence imaging plays essential roles in preclinical drug development by providing important insights into the biodistributions of drugs in vivo with deep tissue penetration and high spatiotemporal resolution. However, NIR-II fluorescence imaging has rarely been exploited for in vivo real-time pharmaceutical evaluations of nanomedicine. Herein, we developed a highly emissive NIR-II luminophore to establish a versatile nanoplatform to noninvasively monitor the in vivo metabolism of nanomedicines bound various polyethylene glycol (PEG) ligands in a real-time manner. An alternative D-A-D conjugated oligomer (DTTB) was synthesized to achieve NIR-II emission peaked at â¼1050 nm with high fluorescence QYs of 13.4% and a large absorption coefficient. By anchoring with the DTTB molecule, intrinsically fluorescent micelles were fabricated and bound with PEG ligands at various chain lengths. In vivo NIR-II fluorescence and photoacoustic imaging results revealed that an appropriate PEG chain length could effectively contribute to the longer blood circulation and better tumor targeting. In vivo therapeutic experiments also confirmed the optimized nanomedicines have efficient photothermal elimination of tumors and good biosafety. This work offered an alternative highly fluorescent NIR-II material and demonstrated a promising approach for real-time pharmaceutical evaluation of nanomedicine in vivo.
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Hipertermia Induzida , Neoplasias , Técnicas Fotoacústicas , Humanos , Ligantes , Nanomedicina , Neoplasias/terapia , Fototerapia , Polietilenoglicóis , Nanomedicina TeranósticaRESUMO
Metal nanozyme has attracted wide interest for biomedicine, and a highly catalytic material in the physiological environment is highly desired. However, catalytic selectivity of nanozyme is still highly challenging, limiting its wide application. Here, we show a trimetallic (triM) nanozyme with highly catalytic activity and environmental selectivity. Enzyme-mimicked investigations find that the triM system possesses multi-enzyme-mimetic activity for removing reactive oxygen species (ROS) and reactive nitrogen species (RNS), such as 1O2, H2O2, â¢OH, and â¢NO. Importantly, triM nanozyme exhibits the significant neutral environment preference for removing the â¢OH, 1O2, and â¢NO free radical, indicating its highly catalytic selectivity. The density functional theory (DFT) calculations reveal that triM nanozyme can capture electrons very easily and provides more attraction to reactive oxygen and nitrogen species (RONS) radicals in the neutral environment. In vitro experiments show that triM nanozyme can improve the viability of injured neural cell. In the LPS-induced brain injury model, the superoxide dismutase (SOD) activity and lipid peroxidation can be greatly recovered after triM nanozyme treatment. Moreover, the triM nanozyme treatment can significantly improve the survival rate, neuroinflammation, and reference memory of injured mice. Present work provides a feasible route for improving selectivity of nanozyme in the physiological environment as well as exploring potential applications in brain science.