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1.
J Nanobiotechnology ; 22(1): 113, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38491372

RESUMO

Wounds are one of the most common health issues, and the cost of wound care and healing has continued to increase over the past decade. In recent years, there has been growing interest in developing innovative strategies to enhance the efficacy of wound healing. Tetrahedral framework nucleic acids (tFNAs) have emerged as a promising tool for wound healing applications due to their unique structural and functional properties. Therefore, it is of great significance to summarize the applications of tFNAs for wound healing. This review article provides a comprehensive overview of the potential of tFNAs as a novel therapeutic approach for wound healing. In this review, we discuss the possible mechanisms of tFNAs in wound healing and highlight the role of tFNAs in modulating key processes involved in wound healing, such as cell proliferation and migration, angiogenesis, and tissue regeneration. The targeted delivery and controlled release capabilities of tFNAs offer advantages in terms of localized and sustained delivery of therapeutic agents to the wound site. In addition, the latest research progress on tFNAs in wound healing is systematically introduced. We also discuss the biocompatibility and biosafety of tFNAs, along with their potential applications and future directions for research. Finally, the current challenges and prospects of tFNAs are briefly discussed to promote wider applications.


Assuntos
Ácidos Nucleicos , Proliferação de Células , Cicatrização
2.
Small ; : e2307256, 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38018326

RESUMO

Removal of invasive bacteria is critical for proper wound healing. This task is challenging because these bacteria can trigger intense oxidative stress and gradually develop antibiotic resistance. Here, the use of a multienzyme-integrated nanocatalytic platform is reported for efficient bacterial clearance and mitigation of inflammatory responses, constructed by physically adsorbing natural superoxide dismutase (SOD), in situ reduction of gold nanoparticles (Au NPs), and incorporation of a DNAzyme on 2D NiCoCu metal-organic frameworks (DNAzyme/SOD/Au@NiCoCu MOFs, termed DSAM), which can adapt to infected wounds. O2 and H2 O2 replenishment is achieved and alleviated the hypoxic microenvironment using the antioxidant properties of SOD. The H2 O2 produced during the reaction is decomposed by peroxidase (POD)-like activity enhanced by Au NPs and DNAzyme, releasing highly toxic hydroxyl radicals (•OH) to kill the bacteria. In addition, it possesses glutathione peroxidase (GPx)-like activity, which depletes GSH and prevents •OH loss. Systematic antimicrobial tests are performed against bacteria using this multienzyme-integrated nanoplatform. A dual-mode strategy involving natural enzyme-enhanced antioxidant capacity and artificial enzyme-enhanced •OH release to develop an efficient and novel enzyme-integrated therapeutic platform is integrated.

3.
Int J Mol Sci ; 24(4)2023 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-36834604

RESUMO

Fighting against bacterial infection and accelerating wound healing remain important and challenging in infected wound care. Metal-organic frameworks (MOFs) have received much attention for their optimized and enhanced catalytic performance in different dimensions of these challenges. The size and morphology of nanomaterials are important in their physiochemical properties and thereby their biological functions. Enzyme-mimicking catalysts, based on MOFs of different dimensions, display varying degrees of peroxidase (POD)-like activity toward hydrogen peroxide (H2O2) decomposition into toxic hydroxyl radicals (•OH) for bacterial inhibition and accelerating wound healing. In this study, we investigated the two most studied representatives of copper-based MOFs (Cu-MOFs), three-dimensional (3D) HKUST-1 and two-dimensional (2D) Cu-TCPP, for antibacterial therapy. HKUST-1, with a uniform and octahedral 3D structure, showed higher POD-like activity, resulting in H2O2 decomposition for •OH generation rather than Cu-TCPP. Because of the efficient generation of toxic •OH, both Gram-negative Escherichia coli and Gram-positive methicillin-resistant Staphylococcus aureus could be eliminated under a lower concentration of H2O2. Animal experiments indicated that the as-prepared HKUST-1 effectively accelerated wound healing with good biocompatibility. These results reveal the multivariate dimensions of Cu-MOFs with high POD-like activity, providing good potential for further stimulation of specific bacterial binding therapies in the future.


Assuntos
Estruturas Metalorgânicas , Staphylococcus aureus Resistente à Meticilina , Animais , Cobre/química , Peróxido de Hidrogênio/química , Antibacterianos/farmacologia
4.
Electrophoresis ; 42(6): 742-748, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33184875

RESUMO

Aging is a fundamental and fascinating process. Anti-aging research tried to find the mysteries about the human lifespan. To investigate the longevity-extending role of caffeic acid phenethylester (CAPE) and reveal the possible regulation mechanism, the long-term cultivation under well-defined environments, real-time monitoring, and live imaging is highly desired. In this paper, a well-designed microfluidic device was proposed to analyze the anti-aging effect of CAPE in Caenorhabditis elegans. With the combined use of multiple functional units, including micro-pillar, worm responder, a branching network of distribution channels, and microchambers, the longitudinal measurements of the exact number of worms throughout the whole lifespans is possible. Meanwhile, the brief cooling function of temperature-controllable system can achieve temporary and repeated immobilization of nematodes for fluorescence imaging. Our research data showed that CAPE can increase the survival of worms under normal and stress condition, including heat stress and paraquat-induced oxidative stress. The further studies revealed the anti-aging mechanism of CAPE. This proposed strategy and device would be a useful platform to facilitate future anti-aging studies and the finding of new lead compounds.


Assuntos
Caenorhabditis elegans , Microfluídica , Envelhecimento , Animais , Ácidos Cafeicos , Longevidade , Estresse Oxidativo
5.
J Cell Biochem ; 120(4): 4813-4826, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-29278652

RESUMO

Cardiac fibrosis is involved in nearly all forms of heart diseases and is characterized by excessive deposition of extracellular matrix proteins by cardiac fibroblasts (CFs). We and others have reported the possibility of poly(ADP-ribose) polymerase 1 (PARP1), the founding subtype of the PARPs enzyme family, as a novel therapeutic target of heart diseases. The cardiac fibrotic induction of mammalian target of rapamycin (mTOR) is mainly due to collagen expression, Smad3- and p53/JNK-mediated apoptosis. However, the possible link between PARP1 and mTOR in the progression of cardiac fibrosis remains unclear. In this study, PARP1 protein expression, and the activity of mTOR and its three target substrates (p70 ribosomal S6 Kinase 1, eukaryotic initiation factor 4E--binding protein 1, and UNC-51-like kinase 1) were augmented; meanwhile, the nicotinamide adenine dinucleotide (NAD) content was significantly reduced in the process of cardiac fibrosis in vivo and in vitro. Sprague-Dawley rats were intraperitoneally injected with 3-aminobenzamide (3AB) (20 mg/kg/d; a well-established PARP1 inhibitor) or rapamycin (Rapa; 1 mg/kg/d; used for mTOR inhibition) 7 days after abdominal aortic constriction (AAC) surgery for 6 weeks. Pretreatment of 3AB or Rapa both relieved AAC-caused cardiac fibrosis and heart dysfunction. Overexpression of PARP1 with adenovirus carrying PARP1 gene specifically transduced into the hearts via intramyocardial multipoint injection caused similar myocardial damage. In CFs, preincubation with PARP1 or mTOR inhibitors all blocked TGF-ß1 induced cardiac fibrosis. PARP1 overexpression evoked cardiac fibrosis, which could be antagonized by mTOR inhibitors or NAD supplementation in CFs. These results provide novel and compelling evidence that PARP1 exacerbated cardiac fibrosis, which was partially attributed to NAD-dependent activation of mTOR.


Assuntos
Cardiopatias/enzimologia , Miocárdio/enzimologia , Poli(ADP-Ribose) Polimerase-1/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Adenoviridae , Animais , Fibrose , Cardiopatias/genética , Cardiopatias/patologia , Masculino , Miocárdio/patologia , Poli(ADP-Ribose) Polimerase-1/genética , Ratos , Ratos Sprague-Dawley , Serina-Treonina Quinases TOR/genética , Transdução Genética
6.
Mikrochim Acta ; 186(6): 374, 2019 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-31123904

RESUMO

An ultrasensitive voltammetric aptasensor was constructed to analyze cardiac troponin I (cTnI). It is based on DNA nanotetrahedron (NTH) linked dual-aptamer (dAPT) and magnetic metal organic frameworks (mMOFs) of type Fe3O4@UiO-66. Firstly, the DNA NTH linked dAPT (Tro4 and Tro6) were immobilized on a gold electrode for improving the capture efficiency of cTnI. The novel mMOFs Fe3O4@UiO-66 was then decorated by Au@Pt nanoparticles (Au@PtNPs), horseradish peroxidase (HRP), G-quadruplex/hemin (GQH) DNAzyme, and two types of aptamers to form signaling nanoprobes. In the presence of cTnI, an aptamer-protein-nanoprobe sandwich-type structure is formed. Afterward, the nanoprobes including enzyme, GQH DNAzyme and Fe3O4@UiO-66/Au@PtNP were utilized to catalyze the oxidation of hydroquinone by hydrogen peroxide for the electrochemical signals amplification, typically at a working potential of -0.1 V (vs. Ag/AgCl). The voltammetric signal increases linearly in the 0.01 to 100 ng·mL-1 cTnI concentration range, and the detection limit is 5.7 pg·mL-1. Graphical abstract An ultrasensitive voltammetric aptasensor was constructed to analyze cardiac troponin I (cTnI) based on DNA nanotetrahedron linked dual-aptamer and magnetic metal organic frameworks of type Fe3O4@UiO-66. The results indicated the aptasensor has a wide linear response range (0.01 to 100 ng/mL) and low detection limit (5.74 pg/mL) for cTnI. GE: gold electrode; MCH: 6-Mmercapto-1-hexanol; HRP: horseradish peroxidase; HQ: hydroquinone; BQ: benzoquinone.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , DNA Catalítico/química , Técnicas Eletroquímicas/métodos , Estruturas Metalorgânicas/química , Troponina I/sangue , Armoracia/enzimologia , Sequência de Bases , DNA Catalítico/genética , Quadruplex G , Ouro/química , Hemina/química , Peroxidase do Rábano Silvestre/química , Humanos , Peróxido de Hidrogênio/química , Hidroquinonas/química , Limite de Detecção , Nanopartículas de Magnetita/química , Oxirredução , Reprodutibilidade dos Testes , Prata/química
7.
Mikrochim Acta ; 185(12): 543, 2018 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-30421038

RESUMO

An ultrasensitive aptasensor is described for the voltammetric determination of the Mycobacterium tuberculosis antigen MPT64 in human serum. Firstly, an amino-modified Zr(IV) based metal-organic framework (MOF; type UiO-66-NH2; made up from Zr6O32 units and 2-amino-terephthalate linkers) with a high specific surface was synthesized and used as the carrier of the gold nanoparticles and the aptamers. Then the signalling nanoprobe was fabricated after the horseradish peroxidase was cast on the nanomaterials. The two aptamers with synergistic effect on binding MPT64 were anchored on the gold electrode. Differential pulse voltammetry indicated that the peak current is highest if the ratio of the two aptamers is 1:1. The assay has a wide linear response range (0.02 to 1000 pg·mL-1 of MPT64) and a 10 fg·mL-1 detection limit at a working potential of around -96 mV (vs Ag/AgCl). The results show this biosensor to be a viable tool for detection of tuberculosis at an early stage. Graphical abstract Schematic presentation of the construction of the nanoprobe and biosensor. Firstly, the surface of UiO-66-NH2 was anchored to gold nanoparticles (AuNPs). A dual-aptamer and HRP were added to form the signalling nanoprobe (Aptamer/HRP/AuNPs/UiO-66-NH2). Then, the aptamers I and II were attached on the surface of gold electrode and 6-mercapto-1-hexanol was used to block the uncovered active site of the gold electrode. Finally, after incubation with MPT64, the signalling nanoprobe was dropped on the modified electrode and the DPV measurements was used for the analysis of Mycobacterium tuberculosis antigen MPT64. (PVP: poly(vinyl pyrrolidone); HRP: horseradish peroxidase; MCH: 6-Mercapto-1-hexanol; HQ: hydroquinone; BQ: benzoquinone).


Assuntos
Antígenos de Bactérias/análise , Aptâmeros de Nucleotídeos/metabolismo , Proteínas de Bactérias/análise , Técnicas Biossensoriais/métodos , Ouro/química , Nanopartículas Metálicas/química , Estruturas Metalorgânicas/química , Peroxidase/metabolismo , Antígenos de Bactérias/sangue , Antígenos de Bactérias/metabolismo , Aptâmeros de Nucleotídeos/genética , Proteínas de Bactérias/sangue , Proteínas de Bactérias/metabolismo , Sequência de Bases , Eletroquímica , Eletrodos , Humanos , Limite de Detecção , Peroxidase/química , Ácidos Ftálicos/química , Zircônio/química
8.
Biochim Biophys Acta ; 1863(12): 3027-3039, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27686254

RESUMO

The Forkhead box-containing protein, O subfamily 3 (FoxO3) transcription factor negatively regulates myocardial hypertrophy, and its transcriptional activity is finely conditioned by diverse posttranslational modifications, such as phosphorylation, acetylation, ubiquitination, methylation and glycosylation. Here, we introduce a novel modification of the FoxO3 protein in cardiomyocytes: poly(ADP-ribosyl)ation (PARylation) mediated by poly(ADP-ribose) polymerase-1 (PARP1). This process catalyzes the NAD+-dependent synthesis of polymers of ADP-ribose (PAR) and their subsequent attachment to target proteins by PARPs. Primary-cultured neonatal rat cardiomyocytes were incubated with isoproterenol (ISO) to induce hypertrophy, or were infected with recombinant adenovirus vectors harboring PARP1 cDNA (Ad-PARP1). Sprague-Dawley (SD) rats were treated with ISO to induce cardiac hypertrophy, or were injected with Ad-PARP1 into the anterior and posterior left ventricular walls. Cardiomyocyte surface area, the mRNA expression of hypertrophic biomarkers, echocardiography, morphometry of the hearts were measured. The PARP1 activity was tested by cellular PAR levels. Interactions of PARP1 and FoxO3 were investigated by co-immunoprecipitation and immunofluorescence technique. PARylation of FoxO3 mediated by PARP1 facilitated its phosphorylation at the T32, S252 and S314 sites, triggered its nucleus export and suppressed its transcriptional activity and target genes expression, ultimately inducing cardiac hypertrophy. Additionally, PARP1 silencing or specific inhibition by 3-Aminobenzamide (3AB) and veliparib (ABT-888) alleviated the inhibition of FoxO3 activity by ISO, thus suppressing ISO-induced cardiac hypertrophy. Our data provide the first evidence that PARP1 exacerbates cardiac hypertrophy by PARylation of FoxO3.


Assuntos
Cardiomegalia/metabolismo , Proteína Forkhead Box O3/metabolismo , Miócitos Cardíacos/metabolismo , Poli(ADP-Ribose) Polimerase-1/metabolismo , Poli Adenosina Difosfato Ribose/metabolismo , Processamento de Proteína Pós-Traducional , Adenoviridae/genética , Adenoviridae/metabolismo , Animais , Animais Recém-Nascidos , Benzamidas/farmacologia , Benzimidazóis/farmacologia , Cardiomegalia/induzido quimicamente , Cardiomegalia/genética , Cardiomegalia/patologia , Ecocardiografia , Proteína Forkhead Box O3/genética , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Isoproterenol , Masculino , Miócitos Cardíacos/citologia , Miócitos Cardíacos/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/antagonistas & inibidores , Poli(ADP-Ribose) Polimerase-1/genética , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Transcrição Gênica
9.
Anal Chem ; 86(16): 8200-5, 2014 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-25054588

RESUMO

In this work, a simple and label-free electrochemical biosensor is developed for microRNA (miRNA) detection on the basis of an arched probe mediated isothermal exponential amplification reaction (EXPAR). The arched probe assembled on the electrode surface consists of two strands that are partially complementary to each other at both ends. The target can hybridize with the complementary sequence of the arched structure, leading to the cleavage of the probe. The strand fixed on the surface of the electrode self-assembles, in the presence of hemin, to G-quadruplex unit, yielding electrochemical signals. The other strand liberated into the solution triggers the EXPAR to recycle and regenerate targets. This method exhibits ultrahigh sensitivity toward miRNA with detection limits of 5.36 fM and a detection range of 3 orders of magnitude. The biosensor is capable of discriminating a single-nucleotide difference between concomitant miRNA and performs well in analyzing crude extractions from cancer cell lines.


Assuntos
Técnicas Eletroquímicas/métodos , MicroRNAs/análise , Linhagem Celular Tumoral , Sondas de DNA/química , Eletrodos , Quadruplex G , Hemina/química , Humanos , Limite de Detecção , Técnicas de Amplificação de Ácido Nucleico/métodos
10.
J Pharmacol Sci ; 125(1): 74-82, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24758922

RESUMO

Autophagy is a highly regulated and multi-step biological process that serves to remove damaged cytoplasmic components and organelles. It has been suggested that the activation of autophagy may be a promising therapeutic strategy for cancer treatment by triggering cell death. In this study, we reported that cyclovirobuxine D (CVB-D), an alkaloid component in a traditional Chinese herb, could induce autophagy in the MCF-7 human breast cancer cell line. CVB-D inhibited the viability of MCF-7 cells in a concentration- and time-dependent manner. Activation of autophagy was characterized by transmission electron microscopy, monodansylcadaverine staining, and expression of autophagy marker microtubule-associated protein 1 light chain 3 (LC3). After CVB-D treatment, a clear accumulation of autophagosomes was observed accompanied with elevated LC3 fluorescent puncta. Western blot analysis revealed that CVB-D significantly promoted the conversion from LC3-I to LC3-II and the expression of autophagy-related protein 5 (ATG5), which are both essential for autophagosome formation. On the other hand, CVB-D-induced autophagy and decrease in cell viability could be blocked by 3-methyladenine, a well-established autophagy inhibitor. Moreover, CVB-D attenuated the phosphorylation of Akt and mTOR, two pivotal suppressors in autophagy pathways. These findings shed new light on the pharmacological actions and mechanism of CVB-D and may support the potential utility of autophagy inducers in cancer treatment.


Assuntos
Autofagia/efeitos dos fármacos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Medicamentos de Ervas Chinesas/química , Transdução de Sinais/efeitos dos fármacos , Adenina/análogos & derivados , Adenina/farmacologia , Autofagia/genética , Proteína 5 Relacionada à Autofagia , Neoplasias da Mama/tratamento farmacológico , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Células MCF-7 , Proteínas Associadas aos Microtúbulos/metabolismo , Terapia de Alvo Molecular , Fosforilação/efeitos dos fármacos , Fitoterapia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismo
11.
Luminescence ; 29(5): 427-32, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23913856

RESUMO

A two-electrode configuration powered by batteries was designed for a microchip capillary electrophoresis-electrochemiluminescence system. A home-made working electrode for end-column mode detection and wall-jet configuration was made up of a platinum wire (0.3 mm diameter) and a quartz capillary (320 µm internal diameter). The platinum wire served as a pseudoreference electrode. The configuration of the detection power supply comprised two D-size batteries (connected in series), a switch, and an adjustable resistor. The microchip consisted of two layers: the bottom layer was a glass sheet containing injection and separation channels; the upper layer was polydimethylsiloxane block. In order to reduce the loss of electrochemiluminescence signal, a coverslip (0.17 mm thickness) was used as the floor of the detection reservoir. The performance of the system was demonstrated by separation and detection of atropine, anisodamine and proline. The linear response for proline ranged from 5 µM to 100 µM (r = 0.9968), and the limit of detection was 1.0 µM (S/N = 3). The system was further applied to the measurement of atropine in atropine sulfate injection solutions with the limit of detection 2.3 µM. This new system is a potential tool in pharmaceutical analysis.


Assuntos
Atropina/análise , Eletroquímica/métodos , Eletroforese Capilar/instrumentação , Medições Luminescentes/métodos , Microfluídica/métodos , Prolina/análise , Alcaloides de Solanáceas/análise , Eletroquímica/instrumentação , Eletrodos , Eletroforese Capilar/métodos , Desenho de Equipamento , Medições Luminescentes/instrumentação , Microfluídica/instrumentação , Platina/química
12.
Adv Healthc Mater ; 13(9): e2303103, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38164814

RESUMO

Programmed death ligand 1 (PD-L1) is highly expressed in cancer cells and participates in the immune escape process of tumor cells. However, as one of the most promising biomarkers for cancer immunotherapy monitoring, the key problem ahead of practical usage is how to effectively improve the detection sensitivity of PD-L1. Herein, an electrochemical aptasensor for the evaluation of tumor immunotherapy is developed based on the immune checkpoint protein PD-L1. The fundamental principle of this method involves the utilization of DNA nanotetrahedron (NTH)-based capture probes and aptamer-modified magnetic metal-organic framework nanocomposites as signaling probes. A synergistic enhancement is observed in the electrocatalytic effect between Fe3O4 and UiO-66 porous shells in Fe3O4@UiO-66 nanocomposites. Therefore, the integration of aptamer-modified Fe3O4@UiO-66@Au with NTH-assisted target immobilization as an electrochemical sensing platform can significantly enhance sensitivity and specificity for target detection. This method enables the detection of targets at concentrations as low as 7.76 pg mL-1 over a wide linear range (0.01 to 1000 ng mL-1). The authors have successfully employed this sensor for in situ characterization of PD-L1 on the cell surface and for monitoring changes in PD-L1 expression during drug therapy, providing a cost-effective yet robust alternative to highly expensive and expertise-dependent flow cytometry.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Estruturas Metalorgânicas , Ácidos Ftálicos , Estruturas Metalorgânicas/química , Antígeno B7-H1 , Proteínas de Checkpoint Imunológico , Limite de Detecção , Técnicas Biossensoriais/métodos , Aptâmeros de Nucleotídeos/química , Fenômenos Magnéticos
13.
Food Chem ; 456: 140039, 2024 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-38906010

RESUMO

Aflatoxin B1 (AFB1) is one of the most toxic mycotoxins and poses a high risk to human health. Highly sensitive and rapid detection is one of the most effective preventive measures to avoid potential hazards. Herein, an electrochemical aptasensor based on DNA nanotetrahedron and zeolitic imidazolate framework-67 loading gold nanoparticles, horseradish peroxidase, and aptamers was designed for the ultrasensitive detection of AFB1. The high specific surface area and large pore volume of zeolitic imidazolate framework-67 can increase the loading capacity and further improve the detection sensitivity of electrochemical aptasensors. DNA nanotetrahedron can enhance the capture ability of AFB1 with steady immobilization. The developed aptasensor showed good analytical performance for AFB1 detection, with a detection limit of 3.9 pg mL-1 and a wide linear range of 0.01-100 ng mL-1. The aptasensor detected AFB1 in corn samples with recovery rates ranging from 94.19%-105.77% and has potential for use in food safety monitoring.

14.
J Colloid Interface Sci ; 661: 520-532, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38308892

RESUMO

Metal-organic frameworks (MOFs) have great potential for combating pathogenic bacterial infections and are expected to become an alternative to antibiotics. However, organic linkers obstruct and saturate the inorganic nodes of MOF structures, making it challenging to utilize the applied potential of metal centers. Here, we combined controlled ligand decarboxylation with noble metal nanoparticles to rationally remodel MIL-53, resulting in a hybrid nanozyme (AgAu@QMIL-53, AAQM) with excellent multiple enzyme-like activities that both eradicate bacteria and promote diabetic wound healing. Specifically, benefitting from oxidase (OXD)-like and peroxidase (POD)-like activities, AAQM converts oxygen (O2) and hydrogen peroxide (H2O2) into superoxide anion radicals (O2-) and hydroxyl radicals (OH) to eradicate bacteria. In in vitro antibacterial experiments, AAQM exhibited favorable killing efficacy against Pseudomonas aeruginosa (P. aeruginosa) and methicillin-resistant Staphylococcus aureus (MRSA) (>99 %). Notably, due to its superoxide (SOD)-like activity and outstanding reactive nitrogen species (RNS) elimination capacity, AAQM can produce adequate O2 and alleviate oxidative stress in diabetic wounds. Benefiting from the rational modification of MIL-53, the synthesized hybrid nanozyme can effectively kill bacteria while alleviating oxidative stress and ultimately promote infected diabetic wound healing. Overall, this biomimetic enzyme-catalyzed strategy will bring enlightenment to the design of self-antibacterial agents for efficient disinfection and wound healing simultaneously.


Assuntos
Diabetes Mellitus , Staphylococcus aureus Resistente à Meticilina , Humanos , Desinfecção , Peróxido de Hidrogênio , Antibacterianos/farmacologia
15.
Bioelectrochemistry ; 149: 108278, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36195024

RESUMO

Zeolitic imidazolate frameworks (ZIFs), a famous subfamily of metal-organic frameworks (MOFs), are considered promising electrocatalysts. Herein, ZIF-67 was selected as an electrocatalyst for designing electrochemical sensors due to having the best electrocatalytic activity in ZIFs. To overcome the insufficient electrocatalytic activity of ZIFs, ZIF-67 derivatives (QZIF-67-X, where X represents calcination time) were obtained by calcining at 250 °C for a certain time. The porous structure of the precursor in QZIF-67-X is maintained, exposing more active centers. QZIF-67-X could accelerate electron transfer and lead to improve the electrocatalytic performance. Moreover, QZIF-67-2 was chosen as an Au nanoparticle-supported nanocarrier to further bind G-quadruplex/hemin DNAzymes with strong catalytic activity due to the best supporting activity of QZIF-67-2 among QZIF-67-X. The synergistic catalysis of QZIF-67-2 and G-quadruplex/hemin DNAzymes effectively amplified the reduction current signal of H2O2. The linear range of the prepared electrochemical sensor was 2 µM-65 mM, and the detection limit was 1.2 µM. Moreover, the real-time detection of H2O2 from HepG2 cells was achieved by the sensor, providing a novel technique for efficient anticancer drug evaluation. These results suggested that QZIF-67 can be utilized as an efficient electrocatalyst for improving the sensitivity of sensors.


Assuntos
Técnicas Biossensoriais , DNA Catalítico , Quadruplex G , Nanopartículas Metálicas , DNA Catalítico/química , Hemina/química , Ouro/química , Peróxido de Hidrogênio/química , Técnicas Eletroquímicas/métodos , Nanopartículas Metálicas/química
16.
J Pharm Anal ; 13(4): 340-354, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37181295

RESUMO

Liquid biopsy is a technology that exhibits potential to detect cancer early, monitor therapies, and predict cancer prognosis due to its unique characteristics, including noninvasive sampling and real-time analysis. Circulating tumor cells (CTCs) and extracellular vesicles (EVs) are two important components of circulating targets, carrying substantial disease-related molecular information and playing a key role in liquid biopsy. Aptamers are single-stranded oligonucleotides with superior affinity and specificity, and they can bind to targets by folding into unique tertiary structures. Aptamer-based microfluidic platforms offer new ways to enhance the purity and capture efficiency of CTCs and EVs by combining the advantages of microfluidic chips as isolation platforms and aptamers as recognition tools. In this review, we first briefly introduce some new strategies for aptamer discovery based on traditional and aptamer-based microfluidic approaches. Then, we subsequently summarize the progress of aptamer-based microfluidics for CTC and EV detection. Finally, we offer an outlook on the future directional challenges of aptamer-based microfluidics for circulating targets in clinical applications.

17.
Food Chem ; 423: 136331, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37182496

RESUMO

In this research, a signal-off electrochemical aptasensor with high sensitivity was constructed for trace detection of zearalenone (ZEN). Specifically, Ce-based metal-organic framework and multi-walled carbon nanotubes nanocomposite was functionalized with polyethyleneimine (P-Ce-MOF@MWCNTs) and served as sensing platform for its high surface area and excellent electrochemical active. Subsequently, toluidine blue (TB) was electrodeposited as the signal probe, and platinum@gold nanoparticles (Pt@Au) were dropped for the attachment of aptamer (ZEA). In the presence of ZEN, the ZEA would specifically recognize and combine with the target, causing a decrease of electrochemical signal from TB. Under the optimal conditions, the aptasensor exhibited good linear relationship for ZEN in a concentration range from 5.0 × 10-5 to 50.0 ng/mL, while the limit of detection (LOD, S/N = 3) and limit of quantitation (LOQ, S/N = 10) were 1.0 × 10-5 ng/mL and 2.9 × 10-5 ng/mL, respectively. Ultimately, the aptasensor was successfully applied into ZEN detection in semen coicis real samples.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , Nanotubos de Carbono , Zearalenona , Zearalenona/análise , Limite de Detecção , Ouro , Técnicas Eletroquímicas
18.
Artigo em Inglês | MEDLINE | ID: mdl-37921634

RESUMO

Metal-organic frameworks (MOFs) with peroxidase (POD)-like activity have great potential for combating drug-resistant bacterial infections. However, the use of POD-like activities is severely limited by low oxygen levels and high levels of glutathione (GSH) within the microenvironment of bacterial infection. Herein, G-quadruplex/hemin DNAzyme-aptamer probes and tannic acid-chelated Au nanoparticle (Au-TA)-decorated Cu-based MOF nanosheets (termed GATC) with triple-enzyme activities were developed for visual detection and efficient antibacterial therapy. First, the monometallic MOFs (Cu-ZIF) showed the best catalytic and loading capacity performance compared with the bimetallic MOFs (CoCu-ZIF and ZnCu-ZIF). Then, Cu-MOFs, Au-TA, and DNAzyme improve the POD-like activity to generate more hydroxyl radicals (•OH) to kill bacteria. GATC can bind to bacteria through aptamer recognition, increasing the bacterial surface contact area for efficient antibacterial activity. GATC can decompose H2O2 into O2 to alleviate hypoxia and improve the microenvironment due to its catalase (CAT)-like activity. In addition, GATC exhibited GSH peroxidase-like activity, which can avoid the loss of •OH and result in bacterial death more easily. Compared with previous studies, GATC exhibited extraordinary bactericidal ability at an extremely low dosage of 3 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA). Notably, the GATC-catalyzed chromogenic reaction could accurately monitor the MRSA infection treatment process. Overall, this work could establish a therapeutic platform for the monitoring and management of bacteria-infected wounds.

19.
Front Chem ; 10: 856003, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35360537

RESUMO

Hydrogen peroxide (H2O2) is the most significant reactive oxygen species in biological systems. Here, we reported an electrochemical sensor for the detection of H2O2 on the basis of bimetallic gold-platinum nanoparticles (Au3Pt7 NPs) supported by Co-based metal organic frameworks (Co-MOFs). First, Au3Pt7 NPs, with optimal electrocatalytic activity and accessible active surface, can be deposited on the surface of the Co-MOF-modified glassy carbon electrodes (Au3Pt7/Co-MOFs/GCE) by one-step electrodeposition method. Then, the electrochemical results demonstrated that the two-dimensional (2D) Co-MOF nanosheets as the supporting material displayed better electrocatalytic properties than the 3D Co-MOF crystals for reduction of H2O2. The fabricated Au3Pt7/2D Co-MOF exhibited high electrocatalytic activity, and the catalytic current was linear with H2O2 concentration from 0.1 µM to 5 mM, and 5-60 mM with a low detection limit of 0.02 µM (S/N = 3). The remarkable electroanalytical performance of Au3Pt7/2D Co-MOF can be attributed to the synergistic effect of the high dispersion of the Au3Pt7 NPs with the marvelous electrochemical properties and the 2D Co-MOF with high-specific surface areas. Furthermore, this sensor has been utilized to detect H2O2 concentrations released from the human Hela cells. This work provides a new method for improving the performance of electrochemical sensors by choosing the proper support materials from diverse crystal morphology materials.

20.
Int J Nanomedicine ; 17: 5947-5990, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36510620

RESUMO

Bacterial-infected wounds are a serious threat to public health. Bacterial invasion can easily delay the wound healing process and even cause more serious damage. Therefore, effective new methods or drugs are needed to treat wounds. Nanozyme is an artificial enzyme that mimics the activity of a natural enzyme, and a substitute for natural enzymes by mimicking the coordination environment of the catalytic site. Due to the numerous excellent properties of nanozymes, the generation of drug-resistant bacteria can be avoided while treating bacterial infection wounds by catalyzing the sterilization mechanism of generating reactive oxygen species (ROS). Notably, there are still some defects in the nanozyme antibacterial agents, and the design direction is to realize the multifunctionalization and intelligence of a single system. In this review, we first discuss the pathophysiology of bacteria infected wound healing, the formation of bacterial infection wounds, and the strategies for treating bacterially infected wounds. In addition, the antibacterial advantages and mechanism of nanozymes for bacteria-infected wounds are also described. Importantly, a series of nanomaterials based on nanozyme synthesis for the treatment of infected wounds are emphasized. Finally, the challenges and prospects of nanozymes for treating bacterial infection wounds are proposed for future research in this field.


Assuntos
Infecções Bacterianas , Nanoestruturas , Infecção dos Ferimentos , Humanos , Infecção dos Ferimentos/tratamento farmacológico , Bactérias , Antibacterianos/uso terapêutico , Nanoestruturas/uso terapêutico
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