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Efficient and accurate acquisition of cellular biomolecular information is crucial for exploring cell fate, achieving early diagnosis, and the effective treatment of various diseases. However, current DNA biosensors are mostly limited to single-target detection, with few complex logic circuits for comprehensive analysis of three or more targets. Herein, we designed a sea anemone-like DNA nanomachine based on DNA strand displacement composed of three logic gates (YES-AND-YES) and delivered into the cells using gold nano bipyramid carriers. The AND gate activation depends on the trigger chain released by upstream DNA strand displacement reactions, while the output signal relies on the downstream DNAzyme structure. Under the influence of diverse inputs (including enzymes, miRNA, and metal ions), the interconnected logic gates simultaneously perform logical analysis on multiple targets, generating a unique output signal in the YES/NO format. This sensor can successfully distinguish healthy cells from tumor cells and can be further used for the diagnosis of different tumor cells, providing a promising platform for accurate cell-type identification.
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DNA Catalítico , Anêmonas-do-Mar , Animais , Anêmonas-do-Mar/genética , DNA/química , DNA Catalítico/química , Lógica , Ouro , Computadores MolecularesRESUMO
The accurate quantification of cancer-derived exosomes, which are emerging as promising noninvasive biomarkers for liquid biopsies in the early diagnosis of cancer, is becoming increasingly imperative. In our work, we developed a magnetically controlled photothermal, colorimetric, and fluorescence trimode aptasensor for human gastric cancer cell (SGC-7901)-derived exosomes. This sensor relied on CP/Mn-PBA DSNBs nanocomposites, created by decorating copper peroxide (CP) nanodots on polyethyleneimine-modified manganese-containing Prussian blue analogues double-shelled nanoboxes (PEI-Mn-PBA DSNBs). Through self-assembly, we attached CD63 aptamer-labeled CP/Mn-PBA DSNBs (Apt-CP/Mn-PBA DSNBs) to complementary DNA-labeled magnetic beads (cDNA-MB). During exosome incubation, these aptamers preferentially formed complexes with exosomes, and we efficiently removed the released CP/Mn-PBA DSNBs by using magnetic separation. The CP/Mn-PBA DSNBs exhibited high photoreactivity and photothermal conversion efficiency under near-infrared (NIR) light, leading to temperature variations under 808 nm irradiation, correlating with different exosome concentrations. Additionally, colorimetric detection was achieved by monitoring the color change in a 3,3',5,5'-tetramethylbenzidine (TMB) system, facilitated by PEI modification, NIR-enhanced peroxidase-like activity of CP/Mn-PBA DSNBs and their capacity to generate Cu2+ and H2O2 under acidic conditions. Moreover, in the presence of Cu2+ and ascorbic acid (AA), DNA sequences could form dsDNA-templated copper nanoparticles (CuNPs), which emitted strong fluorescence at around 575 nm. Increasing exosome concentrations correlated with decreases in temperature, absorbance, and fluorescence intensity. This trimode biosensor demonstrated satisfactory ability in differentiating gastric cancer patients from healthy individuals using human serum samples.
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Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Exossomos , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Cobre , Peróxidos , Peróxido de Hidrogênio , ColorimetriaRESUMO
While designing anisotropic noble metal nanoparticles (NPs) can enhance the signal intensity of Raman dyes, more sensitive surface-enhanced Raman scattering (SERS) probes can be designed by oriented self-assembly of noble metal nanomaterials into dimers or higher-order nanoclusters. In this study, we engineered a self-assembly strategy in living cells for real-time fluorescence and SERS dual-channel detection of intracellular microRNAs (miRNAs), using Mg2+-dependent 8-17E DNAzyme sequences as the driving motors, gold nanocubes (AuNCs) as the driver components, and three-branched double-stranded DNA as the linking tool. The assembly selects adenine in DNA as a reporter molecule, simplifying the labeling process of Raman reporter molecules and reducing the synthesis process. In addition, adenine is stably distributed between the faces of AuNCs and the wide hotspot region gives good reproducibility of the adenine SERS signal. In this strategy, the SERS channel was consistently stable and more sensitive compared to the fluorescence channel. Among them, the detection limit of the SERS channel was 2.1 pM and the coefficient of variation was 1.26% in the in vitro liquid phase and 1.49% in MCF-7 cells. The strategy successfully achieved accurate tracking and quantification of miRNA-21 in cancer cells, showing good reproducibility in complex samples as well as cells. The reported strategy provides ideas for exploring intracellular specific triggering of nanoparticles for precise control of self-assembly.
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Ouro , Nanopartículas Metálicas , MicroRNAs , Análise Espectral Raman , Ouro/química , MicroRNAs/análise , Humanos , Nanopartículas Metálicas/química , Células MCF-7 , Fluorescência , Propriedades de SuperfícieRESUMO
Cuproptosis, a recently discovered copper-dependent cell death, presents significant potential for the development of copper-based nanoparticles to induce cuproptosis in cancer therapy. Herein, a unique ternary heterojunction, denoted as HACT, composed of core-shell Au@Cu2O nanocubes with surface-deposited Titanium Dioxide quantum dots and modified with hyaluronic acid is introduced. Compared to core-shell AC NCs, the TiO2/Au@Cu2O exhibits improved energy structure optimization, successfully separating electron-hole pairs for redox use. This optimization results in a more rapid generation of singlet oxygen and hydroxyl radicals triggering oxidative stress under ultrasound radiation. Furthermore, the HACT NCs initiate cuproptosis by Fenton-like reaction and acidic environment, leading to the sequential release of cupric and cuprous ions. This accumulation of copper induces the aggregation of lipoylated proteins and reduces iron-sulfur proteins, ultimately initiating cuproptosis. More importantly, HACT NCs show a tendency to selectively target cancer cells, thereby granting them a degree of biosecurity. This report introduces a ternary heterojunction capable of triggering both cuproptosis and oxidative stress-related combination therapy in a stimulus-responsive manner. It can energize efforts to develop effective melanoma treatment strategies using Cu-based nanoparticles through rational design.
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Nanozymes, serving as synthetic alternatives to natural enzymes, offer several benefits including cost-effectiveness, enzyme-like catalytic abilities, enhanced stability, adjustable catalytic activity, easy recyclability, mild reaction conditions, and environmental friendliness. Nonetheless, the ongoing quest to develop nanozymes with enhanced activity and to delve into the catalytic mechanism remains a challenge. In our research, we effectively developed Au@CuO nanocomposites (Au@CuO Nc), replicating the functions of four enzymes found in nature: peroxidase (POD), catalase (CAT), glutathione peroxidase (GPx), and oxidase (OXD). The catalytic efficiency of Au@CuO Nc for TMB oxidation (oxTMB) was approximately 4.8 times greater than that of plain Cu2O cubes, attributed to the synergistic catalytic impact between the Au element and Cu2O within Au@CuO Nc. Mechanistic studies revealed that the novel Au@CuO Nc nanozyme greatly enhances the decomposition of H2O2 to reactive oxygen species (ROS) intermediates (ËOH, ËO2- and 1O2), resulting in increased POD-like activity of the single-component Cu2O cubes. When an antioxidant like TA was added to the chromogenic system, it converted oxTMB into a colorless form of TMB, enabling further evaluation of TA. Hence, a colorimetric sensor was developed for the rapid and precise quantitative measurement of TA, demonstrating strong linearity between 0.3 and 2.4 µM and featuring a low detection threshold of 0.25 µM. Moreover, this sensor was effectively utilized for the assessment of TA in actual tea samples. This work innovatively proposes a simplified and reliable strategy for the advanced design of highly effective Cu-based nanozymes, enhancing enzyme-like reactions for simultaneous, on-site colorimetric probing of antioxidants.
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The programmed cell death (PCD) pathway removes functionally insignificant, infection-prone, or potentially tumorigenic cells, underscoring its important role in maintaining the stability of the internal environment and warding off cancer and a host of other diseases. PCD includes various forms, such as apoptosis, copper death, iron death, and cellular pyroptosis. However, emerging solid-state electron-mediated Z-scheme heterostructured semiconductor nanomaterials with high electron-hole (e-h+) separation as a new method for inducing PCD have not been well studied. We synthesize the Bi2S3-Bi2O3-Au-PEG nanorods (BB-A-P NRs) Z-scheme heterostructured semiconductor has a higher redox capacity and biocompatibility. Firstly, the BB-A-P NRs are excited by near-infrared (NIR) light, which mimics the action of catalase by supplying oxygen (O2) and converting it to a single-linear state of oxygen (1O2) via e-h+ transfer. Secondly, they react with hydrogen peroxide (H2O2) and water (H2O) in tumor to produce hydroxyl radicals (â¢OH), inducing apoptosis. Intriguingly, the Caspase-1/Gasdermin D (GSDMD)-dependent conventional pyroptosis pathway induced cellular pyroptosis activated by apoptosis and reactive oxygen species (ROS) which causes the intense release of damage associated molecular patterns (DAMPs), leading to the inflammatory death of tumor cells. This, in turn, activates the immunological environment to achieve immunogenic cell death (ICD). BB-A-P enables computed tomography imaging, which allows for visualization of the treatment. BB-A-P activated dual PCD can be viewed as an effective mode of cell death that coordinates the intracellular environment, and the various pathways are interrelated and mutually reinforcing which shows promising therapeutic effects and provides a new strategy for eliminating anoxic tumors.
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Apoptose , Semicondutores , Animais , Apoptose/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral , Elétrons , Humanos , Melanoma/patologia , Nanotubos/química , Nanoestruturas/química , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio , Bismuto/química , Piroptose/efeitos dos fármacos , Ouro/químicaRESUMO
Zinc oxide nanoparticles (ZnO NPs) stand as among the most significant metal oxide nanoparticles in trigger the formation of reactive oxygen species (ROS) and induce apoptosis. Nevertheless, the utilization of ZnO NPs has been limited by the shallowness of short-wavelength light and the constrained production of ROS. To overcome these limitations, a strategy involves achieving a red shift towards the near-infrared (NIR) light spectrum, promoting the separation and restraining the recombination of electron-hole (e--h+) pairs. Herein, the hybrid plasmonic system Au@ZnO (AZ) with graphene quantum dots (GQDs) doping (AZG) nano heterostructures is rationally designed for optimal NIR-driven cancer treatment. Significantly, a multifold increase in ROS generation can be achieved through the following creative initiatives: (i) plasmonic Au nanorods expands the photocatalytic capabilities of AZG into the NIR domain, offering a foundation for NIR-induced ROS generation for clinical utilization; (ii) elaborate design of mesoporous core-shell AZ structures facilitates the redistribution of electron-hole pairs; (iii) the incorporation GQDs in mesoporous structure could efficiently restrain the recombination of the e--h+ pairs; (iv) Modification of hyaluronic acid (HA) can enhance CD44 receptor mediated targeted triple-negative breast cancer (TNBC). In addition, the introduced Au NRs present as catalysts for enhancing photothermal therapy (PTT), effectively inducing apoptosis in tumor cells. The resulting HA-modified AZG (AZGH) exhibits efficient hot electron injection and e--h+ separation, affording unparalleled convenience for ROS production and enabling NIR-induced PDT for the cancer treanment. As a result, our well-designed mesoporous core-shell AZGH hybrid as photosensitizers can exhibit excellent PDT efficacy.
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Ouro , Grafite , Estresse Oxidativo , Pontos Quânticos , Espécies Reativas de Oxigênio , Neoplasias de Mama Triplo Negativas , Óxido de Zinco , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Feminino , Linhagem Celular Tumoral , Ouro/química , Grafite/química , Óxido de Zinco/química , Animais , Pontos Quânticos/química , Camundongos , Nanopartículas Metálicas/química , Apoptose/efeitos dos fármacos , Ácido Hialurônico/química , ElétronsRESUMO
Piezoelectric material-mediated sonodynamic therapy (SDT) has received considerable research interest in cancer therapy. However, the simple applications of conventional piezoelectric materials do not realize the full potential of piezoelectric materials in medicine. Therefore, the energy band structure of a piezoelectric material is modulated in this study to meet the actual requirement for cancer treatment. Herein, an elaborate PEGylated piezoelectric solid solution 0.7BiFeO3 -0.3BaTiO3 nanoparticles (P-BF-BT NPs) is synthesized, and the resultant particles achieve excellent piezoelectric properties and their band structure is tuned via band engineering. The tuned band structure of P-BF-BT NPs is energetically favorable for the synchronous production of superoxide radicals (â¢O2 - ) and oxygen (O2 ) self-supply via water splitting by the piezoelectric effect. Besides, the P-BF-BT NPs can initiate the Fenton reaction to generate hydroxyl radical (â¢OH), and thus, chemodynamic therapy (CDT) can be augmented by ultrasound. Detailed in vitro and in vivo research has verified the promising effects of multimodal imaging-guided P-BF-BT NP-mediated synergistic SDT/CDT by the piezo-Fenton process in hypoxic tumor elimination, accompanied by high therapeutic biosafety. The current demonstrates a novel strategy for designing and synthesizing "custom-made" piezoelectric materials for cancer therapy in the future.
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Nanopartículas , Neoplasias , Humanos , Engenharia , Radical Hidroxila , Hipóxia , Oxigênio , Linhagem Celular Tumoral , Neoplasias/terapia , Peróxido de HidrogênioRESUMO
Due to the inherent low immunogenicity and immunosuppressive tumor microenvironment (TME) of malignant cancers, the clinical efficacy and application of tumor immunotherapy have been limited. Herein, a bimetallic drug-gene co-loading network (Cu/ZIF-8@U-104@siNFS1-HA) is developed that increased the intracellular labile iron pool (LIP) and enhanced the weakly acidic TME by co-suppressing the dual enzymatic activities of carbonic anhydrase IX (CA IX) and cysteine desulfurylase (NFS1), inducing a safe and efficient initial tumor immunogenic ferroptosis. During this process, Cu2+ is responsively released to deplete glutathione (GSH) and reduce the enzyme activity of glutathione peroxidase 4 (GPX4), achieving the co-inhibition of the three enzymes and further inducing lipid peroxidation (LPO). Additionally, the reactive oxygen species (ROS) storm in target cells promoted the generation of large numbers of double-stranded DNA breaks. The presence of Zn2+ substantially increased the expression of cGAS/STING, which cooperated with ferroptosis to strengthen the immunogenic cell death (ICD) response and remodel the immunosuppressive TME. In brief, Cu/ZIF-8@U-104@siNFS1-HA linked ferroptosis with immunotherapy through multiple pathways, including the increase in LIP, regulation of pH, depletion of GSH/GPX4, and activation of STING, effectively inhibiting cancer growth and metastasis.
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Alzheimer's disease (AD) is a severe neurodegenerative condition characterized by inflammation, beta-amyloid (Aß) plaques, and neurodegeneration, which currently lack effective treatments. Chiral nanomaterials have emerged as a promising option for treating neurodegenerative disorders due to their high biocompatibility, strong sustained release ability, and specific enantiomer selectivity. The development of a stimulus-responsive chiral nanomaterial, UiO-66-NH2 @l-MoS2 QDs@PA-Ni (MSP-U), for the treatment of AD is reported. MSP-U is found to stimulate neural stem cell (NSCs) differentiation, promote in situ hydrogen (H2 ) production, and clear Aß plaques. l-MoS2 QDs modified with l-Cysteine (l-Cys) effectively enhance the differentiation of NSCs into neurons through circularly polarized near-infrared radiation. Doped-phytic acid nickel (PA-Ni) improves the activity of l-MoS2 QDs in scavenging reactive oxygen species at the lesion site via photocatalytic H2 production. Loading l-MoS2 QDs with UiO-66 type metal oxide suppresses electron-hole recombination effect, thereby achieving rapid charge separation and improving transport of photogenerated electrons, leading to significantly improved H2 production efficiency. The photothermal effect of MSP-U also clears the generated Aß plaques. In vivo evaluations show that MSP-U improves spatial cognition and memory, suggesting a promising potential candidate for the treatment of AD using chiral nanomaterials.
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Doença de Alzheimer , Ácidos Ftálicos , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Molibdênio/farmacologia , Peptídeos beta-Amiloides/metabolismo , CogniçãoRESUMO
Microplastics (MPs) have been shown to be a new type of pollutant in the oceans, with complex biofilms attached to their surfaces. Bacteria with quorum sensing (QS) systems are important participants in biofilms. Such bacteria can secrete and detect signal molecules. When a signal molecule reaches its threshold level, bacteria with QS systems can perform several biological functions, such as biofilm formation and antibiotic metabolite production. However, the ecological effects of QS bacteria in biofilm as MPs distribute globally with ocean currents are not to be elucidate yet. In this study, polypropylene and polyvinyl chloride were selected for on-site enrichment to acquire microplastics with biofilms. Eight culturable QS bacteria in the resulting biofilm were isolated by using biosensor assays, and their biodiversity was analyzed. The profiles of the N-acyl-homoserine lactones (AHLs) produced by these bacteria were analyzed by using thin-layer chromatography (TLC)-bioautography and gas chromatography and mass spectrometry (GC-MS). Biofilm-forming properties and several biological characteristics, such as bacteriostasis, algal inhibition, and dimethylsulfoniopropionate (DMSP) degradation, were explored along with QS quenching. Results showed that QS bacteria were mainly affiliated with class Alphaproteobacteria, particularly Rhodobacteraceae, followed by class Gammaproteobacteria. TLC-bioautography and GC-MS analyses revealed that seven AHLs, namely, C6-HSL, C8-HSL, 3-oxo-C6-HSL, 3-oxo-C8-HSL, 3-oxo-C10-HSL, and two unidentified AHLs were produced. The QS system equipped bacteria with strong biofilm-forming capacity and may contribute to the keystone roles of Rhodobacteraceae. In addition, QS bacteria may exacerbate the adverse environmental effects of MPs, such as inducing the misfeeding of planktons on MPs. This study elucidated the diversity of QS bacteria in MP-associated biofilms and provided a new perspective of the effect of key membrane-forming bacteria on the marine ecological environment.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Percepção de Quorum , Acil-Butirolactonas , Bactérias , Biodiversidade , Biofilmes , Ecossistema , Microplásticos , Plásticos , AnimaisRESUMO
Compared with the single-marker detection scheme, the detection of multiple targets in the complex cell and biological environment can obtain more reliable detection results. Herein, we detected miRNA-21 and APE1 in two modes, AND and OR, respectively, based on gold nanoflares and simple logic components. In both modes, DNAzyme and APE1 can get rich fluorescence recovery results by breaking the DNA strands from the gold nanorods (AuNRs) and unquenching under different conditions. In vivo and in vitro experiments suggest that both nanoflares exhibit excellent biocompatibility and make efficient and sensitive judgments on the two targets. This strategy emphasizes the reuse nature of enzymes, and a small amount of target can generate a large amount of fluorescent signal in the logic device, which greatly reduces the detection limit when monitoring low-abundance targets. Since the short-stranded DNA component of the detection device is simple in composition and easy to program its probe sequence, it can be expanded into a detection system for the detection of other sets of related markers, which increases its potential for clinical application.
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Técnicas Biossensoriais , DNA Catalítico , Nanopartículas Metálicas , Biomarcadores Tumorais , Técnicas Biossensoriais/métodos , DNA , Ouro , LógicaRESUMO
As living standards rise, the demand for high-quality chilled meat among consumers also grows. Researchers and enterprises have been interested in ensuring the quality of chilled meat in all links of the downstream industry. Nanozyme has shown the potential to address the aforementioned requirements. Reasons and approaches for the application of nanozymes in the freshness assessment or shelf life extension of chilled meat were discussed. The challenges for applying these nanozymes to ensure the quality of chilled meat were also summarized. Finally, this review examined the safety, regulatory status, and consumer attitudes toward nanozymes. This review revealed that the freshness assessment of chilled meat is closely related to mimicking the enzyme activities of nanozymes, whereas the shelf life changes of chilled meat are mostly dependent on the photothermal activities and pseudophotodynamic activities of nanozymes. In contrast, studies regarding the shelf life of chilled meat are more challenging to develop, as excessive heat or reactive oxygen species impair its quality. Notably, meat contains a complex matrix composition that may interact with the nanozyme, reducing its effectiveness. Nanopollution and mass manufacturing are additional obstacles that must be overcome. Therefore, it is vital to choose suitable approaches to ensure meat quality. Furthermore, the safety of nanozymes in meat applications still needs careful consideration owing to their widespread usage.
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A multifunctional theranostic nanosystem that integrates dynamic monitoring and therapeutic functions is necessary for precision tumor medicine. Herein, an entropy-driven self-assembly nanomachine is developed that overcomes the mechanism differences of different diagnostic modes and is applied to miRNA surface-enhanced Raman scattering (SERS)-fluorescence dual-mode dynamic monitoring and synergy phototherapy. It is worth noting that the activated dual-mode theranostic nanosystem (DTN) is capable of tumor in situ fluorescence imaging and SERS absolute quantification of the target. After being internalized into tumor cells, the DTN nanosystem is activated by the DNA cascade chain displacement of the target miR-21, resulting in the secondary release of fluorophores and the assembly of core-satellite structures (CS structures). The coupling of localized surface plasmon resonances (LSPRs) in the CS structure results in the formation of numerous enhanced electric fields (hot spot) in the nanogap of the CS structure. Then the DTN nanosystem greatly improves the sensitivity and repeatability of Raman detection by converting trace targets into numerous adenines residing in the electromagnetic hot spot of the CS structure. Meanwhile, the CS structure and the loaded photosensitizer are used for synergy phototherapy under the guidance of fluorescence imaging. This proposed strategy is confirmed by in vivo and in vitro results, and it provides new ideas for tumor SERS-fluorescence dual-mode diagnosis and effective tumor therapy.
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MicroRNAs , Nanoestruturas , Ouro , Fototerapia , Análise Espectral RamanRESUMO
Despite several attempts, incorporating biological detection that supplies necessary biological information into therapeutic nanotheranostics for hypoxic tumor treatments is considered to be in its infancy. It is therefore imperative to consolidate biological detection and desirable phototherapy into a single nanosystem for maximizing theranostic advantages. Herein, we develop a versatile nanoprobe through combined fluorescence resonance energy transfer (FRET) and oxygen-augmenting strategy, namely APT, which enables glycosylation detection, O2 self-sufficiency, and collaborative phototherapy. Such APT nanoprobes were constructed by depositing platinum onto gold nano-bipyramids (Au NBPs), linking FITC fluorophore-labeled AS1411 aptamers for introducing FRET donors, and by conjugating G-quadruplex intercalated with TMPyP4 to their surfaces via the SH-DNA chain. By installing FRET acceptors on the glycan of targeted EpCAM glycoprotein using the metabolic glycan labeling and click chemistry, FRET signals appear on the cancerous cell membranes, not normal cells, when donors and acceptors are within an appropriate distance. This actualizes protein-specific glycosylation visualization while revealing glycan-based changes correlated with tumor progression. Interestingly, the deposited platinum scavenges excessive H2O2 as artificial nanoenzymes to transform O2 that alleviates tumor hypoxia and simultaneously elevates singlet oxygen (1O2) for inducing cancer cell apoptosis. Notably, the significant hyperthermia devastation was elicited via APT nanoprobes with phenomenal photothermal therapy (PTT) efficiency (71.8%) for thermally ablating cancer cells, resulting in synergistically enhanced photodynamic-hyperthermia therapy. Consequently, APT nanoprobes nearly actualized thorough tumor ablation while demonstrating highly curative biosafety. This work offers a new paradigm to rationally explore a combined FRET and oxygen-augmenting strategy with a focus on nanotheranostics for hypoxic tumor elimination.
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Ouro , Neoplasias , Linhagem Celular Tumoral , Transferência Ressonante de Energia de Fluorescência , Humanos , Peróxido de Hidrogênio , Neoplasias/terapia , Oxigênio , FototerapiaRESUMO
Superfluous zinc ion (Zn2+) in living cells has been identified as a potential tumor biomarker for early cancer diagnosis and cancer progression monitoring. In this paper, we developed a novel carbon nanohorns/Pt nanoparticles/DNA (CNHs/Pt NPs/DNA) nanoplatform based on the clamped hybridization chain reaction (c-HCR) process for intracellular Zn2+ imaging and enhanced cooperative phototherapy of cancer cells. Cross-shaped DNAzyme (c-DNAzyme), hairpin DNA1, hairpin DNA2, and aptamer DNA were adsorbed onto the surfaces of CNHs/Pt NPs, and the fluorescence of carboxytetramethyl-rhodamine was also quenched. After entering the living cells, the c-DNAzyme was cleaved to output trigger DNA in the existence of intracellular Zn2+ and initiate the c-HCR process for fluorescence amplification. Compared with the single HCR process triggered by a single DNAzyme, the c-HCR process could further improve the amplification efficiency and sensitivity. In addition, such a nanoprobe possesses a catalysis-enhanced photodynamic effect by Pt NP generation of oxygen in a tumor microenvironment and increases the photothermal effect by loading of Pt NPs on CNHs, indicating that this is a promising biological method for cancer diagnosis and cancer cell therapy.
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Carbono/química , DNA/química , Nanopartículas Metálicas/química , Imagem Molecular/métodos , Fototerapia/métodos , Platina/química , Zinco/metabolismo , Células HeLa , Humanos , Espaço Intracelular/metabolismoRESUMO
Amyloid ß-peptide oligomer (AßO) is widely acknowledged as the promising biomarker for the diagnosis of Alzheimer's disease (AD). In this work, we designed a three-dimensional (3D) DNA walker nanoprobe for AßO detection and real-time imaging in living cells and in vivo. The presence of AßO triggered the DNAzyme walking strand to cleave the fluorophore (TAMRA)-labeled substrate strand modified on the gold nanoparticle (AuNP) surface and release TAMRA-labeled DNA fragment, resulting in the recovery of fluorescent signal. The entire process was autonomous and continuous, without external fuel strands or protease, and finally produced plenty of TAMRA fluorescence, achieving signal amplification effect. The nanoprobe enabled the quantitative detection of AßO in vitro, and the limit of detection was 22.3 pM. Given the good biocompatibility of 3D DNA walker nanoprobe, we extended this enzyme-free signal amplification method to real-time imaging of AßO. Under the microscope, nanoprobe accurately located and visualized the distribution of AßO in living cells. Moreover, in vivo imaging results showed that our nanoprobe could be used to effectively distinguish the AD mice from the wild-type mice. This nanoprobe with the advantages of great sensitivity, high specificity, and convenience, provides an outstanding prospect for AD's early diagnosis development.
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Peptídeos beta-Amiloides/análise , DNA Catalítico/metabolismo , DNA/química , Nanopartículas Metálicas/química , Microscopia Confocal/métodos , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/química , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Linhagem Celular , DNA/metabolismo , DNA Catalítico/química , Modelos Animais de Doenças , Corantes Fluorescentes/química , Ouro/química , Limite de Detecção , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Imagem Óptica/métodos , Rodaminas/química , Zinco/químicaRESUMO
Integrating biological detection and treatment into one system is a smart therapeutic maneuver for efficient cancer treatment. Herein, a target-activated core-satellite nanostructure (CS nanostructure) assembly built on gold nanobipyramids motor (AuNBPs motor)/gold nanoparticle probe (AuNP probe) exhibiting simultaneous dual signal-on imaging, quantification of intracellular microRNA-21 (miR-21), and photothermal therapy (PTT) for cancer is designed. Of note, when the AuNBPs motor/AuNP probe enters into cells, miR-21 triggers the reaction between AuNBPs motor and AuNP probe, resulting in the formation of CS nanostructure assembly. The process of assembling the CS nanostructure is accompanied with strong fluorescent signals from TAMRA and surface-enhanced Raman scattering (SERS) signals from adenine. The fluorescent signal is leveraged to image the intracellular miR-21 level, whereas the SERS signal is utilized for absolute quantification of intracellular miR-21, and the CS nanostructure acts as the photosensitizer for PTT. This strategy can successfully image and quantify miR-21 in a single cell, and also distinguish normal cells from tumor cells. Moreover, under the guidance of fluorescence signal, the assembly kills tumor cells and inhibits tumor growth via PTT. In vitro and in vivo results prove that the proposed strategy possesses enormous potential for application in the diagnosis and treatment of cancer.
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Nanopartículas Metálicas , MicroRNAs , Nanoestruturas , Ouro , Imagem Óptica , Terapia Fototérmica , Análise Espectral RamanRESUMO
For the precise treatment of tumors, it is necessary to develop a theranostic nanoplatform that has both diagnostic and therapeutic functions. In this article, we designed a new theranostic probe for fluorescence imaging of Zn2+ and fluorescence/MRI guided magnetically targeted photodynamic-photothermal therapy. The fluorescence imaging of Zn2+ was based on an endogenous ATP-driven DNA nanomachine that could perform repetitive stand displacement reaction. It modifies all units on a single PDA/Fe3O4 nanoparticle containing a hairpin-locked initiated strand activated by a target molecule in cells, a two-stranded fuel DNA triggered by ATP, and a two-stranded DNA track responding to an initiated strand and fuel DNA. After entering the cell, the intracellular target Zn2+ initiates the nanomachine via an autocatalytic cleavage reaction, and the machine programmatically and gradually runs on the assembled DNA track via fuel DNA driving and the intramolecular toehold-mediated stand displacement reaction. The Fe3O4 core first exhibits magnetic targeting, increasing the ability of nanoparticles to enter tumor cells at the tumor site. The Fe3O4 could also be employed as a powerful magnetic resonance imaging (MRI) contrast agent and guided therapy. Using 808 nm laser and 635 nm laser irradiation together at the tumor site, the PDA nanoshell produced an excellent photothermal effect and the TMPyP4 molecules entering the cell generated reactive oxygen species, followed by cell damage. A series of reliable experiments suggested that the Fe3O4@PDA@DNA nanoprobe showed superior fluorescence specificity, MRI, a remarkable photothermal/photodynamic therapy effect, and favorable biocompatibility. This theranostic nanoplatform offered a split-new insight into tumor fluorescence and MRI diagnosis as well as effective tumor therapy.
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DNA/química , Óxido Ferroso-Férrico/química , Indóis/química , Imageamento por Ressonância Magnética , Imagem Óptica , Fotoquimioterapia/métodos , Polímeros/química , Zinco/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Estudos de Viabilidade , Humanos , Espaço Intracelular/metabolismo , Células MCF-7 , Camundongos , Nanomedicina TeranósticaRESUMO
A multifunctional nanoplatform that enables the integration of biological detection, imaging diagnosis, and synergistic therapy into a single nanostructure holds great promise for nanoscience and nanomedicine. Herein, a novel theranostic platform was presented for label-free imaging of cell surface glycans based on DNA/silver nanoclusters (AgNCs) via hybridization chain reaction (HCR) and fluorescence guided photothermal therapy (PTT). In this strategy, a dibenzocyclooctyne (DBCO)-functionalized DNA and two hairpin structures of DNA/AgNCs probes were involved. Following metabolic glycan labeling, the binding of DBCO-functionalized DNA to cell surface initiated HCR, and then cell surface glycans were specifically labeled by DNA/AgNCs fluorescent probes. Furthermore, this signal amplification strategy was adopted in quantitative analysis, and the detection limit could be achieved as low as 20 cells in 200 µL of binding buffer. Moreover, the remarkable photothermal properties of DNA/AgNCs via HCR led to efficient killing of cancer cells and inhibited the tumor growth under imaging guide. In this strategy, DNA/AgNCs were utilized to detect the cellular glycans, which aided in overcoming the high cost and instability of fluorescent dyes. Simultaneously, the HCR process avoided the introduction of excessive azido-sugars under the precondition of ensuring apparent fluorescence. These results indicated that the developed nanoplatform has great potential for specific cell surface glycans imaging and fluorescence guided PTT.