RESUMO
Harnessing the programmable nature of DNA origami for controlling structural features in crystalline materials affords opportunities to bring crystal engineering to a remarkable level. However, the challenge of crystallizing a single type of DNA origami unit into varied structural outcomes remains, given the requirement for specific DNA designs for each targeted structure. Here, we show that crystals with distinct equilibrium phases and shapes can be realized using a single DNA origami morphology with an allosteric factor to modulate the binding coordination. As a result, origami crystals undergo phase transitions from a simple cubic lattice to a simple hexagonal (SH) lattice and eventually to a face-centered cubic (FCC) lattice. After selectively removing internal nanoparticles from DNA origami building blocks, the body-centered tetragonal and chalcopyrite lattice are derived from the SH and FCC lattices, respectively, revealing another phase transition involving crystal system conversions. The rich phase space was realized through the de novo synthesis of crystals under varying solution environments, followed by the individual characterizations of the resulting products. Such phase transitions can lead to associated transitions in the shape of the resulting products. Hexagonal prism crystals, crystals characterized by triangular facets, and twinned crystals are observed to form from SH and FCC systems, which have not previously been experimentally realized by DNA origami crystallization. These findings open a promising pathway toward accessing a rich phase space with a single type of building block and wielding other instructions as tools to develop crystalline materials with tunable properties.
Assuntos
Nanopartículas Metálicas , Nanoestruturas , Nanopartículas Metálicas/química , Magnésio , DNA/química , Cristalização , Transição de Fase , Nanotecnologia , Conformação de Ácido Nucleico , Nanoestruturas/químicaRESUMO
Precise mapping and regulation of cell surface receptors hold immense significance in disease treatment, such as cancer, infection, and neurodisorders, but also face enormous challenges. In this study, we designed a series of adjustable multivalent aptamer-based DNA nanostructures to precisely control their interaction with receptors in tumor cells. By profiling surface receptors on 12 cell lines using 10 different aptamers, we generated a heatmap that accurately distinguished between various tumor types based on multiple markers. We then incorporated these aptamers onto DNA origami structures to regulate receptor recognition, with patch-like structures demonstrating a tendency to be trapped on the cell surface and with tube-like structures showing a preference for internalization. Through precise control of aptamer species, valence, and geometric patterns, we found that multiheteroreceptor-mediated recognition not only favored the specific binding of nanostructures to tumor cells but also greatly enhanced intracellular uptake by promoting clathrin-dependent endocytosis. Specifically, we achieved over 5-fold uptake in different tumor cells versus normal cells using tube-like structures modified with different diheteroaptamer pairs, facilitating targeted drug delivery. Moreover, patch-like structures with triheteroaptamers guided specific interactions between macrophages and tumor cells, leading to effective immune clearance. This programmable multivalent system allows for the precise regulation of cell recognition using multiple parameters, demonstrating great potential for personalized tumor treatment.
Assuntos
Aptâmeros de Nucleotídeos , Nanoestruturas , Neoplasias , Humanos , Aptâmeros de Nucleotídeos/química , Neoplasias/tratamento farmacológico , Nanoestruturas/química , Sistemas de Liberação de Medicamentos , DNA/química , Linhagem Celular TumoralRESUMO
Simultaneous profiling of redox-regulated markers at different cellular sublocations is of great significance for unraveling the upstream and downstream molecular mechanisms of oxidative stress in living cells. Herein, by synchronizing dual target-triggered DNA machineries in one nanoentity, we engineered a DNA walker-driven mass nanotag (MNT) assembly system (w-MNT-AS) that can be sequentially activated by oxidative stress-associated mucin 1 (MUC1) and apurinic/apyrimidinic endonuclease 1 (APE1) from plasma membrane to cytoplasm and induce recycled assembly of MNTs for multiplex detection of the two markers by matrix-assisted laser desorption ionization mass spectrometry (MALDI MS). In the working cascade, the sensing process governs the separate activation of w-MNT-AS by MUC1 and APE1 in diverse locations, while the assembly process contributes to the parallel amplification of the ion signal of the characteristic mass tags. In this manner, the differences between MCF-7, HeLa, HepG2, and L02 cells in membrane MUC1 expression and cytoplasmic APE1 activation were fully characterized. Furthermore, the oxidative stress level and dynamics caused by exogenous H2O2, doxorubicin, and simvastatin were comprehensively demonstrated by tracking the fate of the two markers across different cellular locations. The proposed w-MNT-AS coupled MS method provides an effective route to probe multiple functional molecules that lie at different locations while participating in the same cellular event, facilitating the mechanistic studies on cellular response to oxidative stress and other disease-related cellular processes.
Assuntos
DNA Liase (Sítios Apurínicos ou Apirimidínicos) , DNA , Mucina-1 , Estresse Oxidativo , Humanos , Mucina-1/metabolismo , DNA/metabolismo , DNA/química , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/metabolismo , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Peróxido de Hidrogênio/metabolismoRESUMO
Several major viral pandemics in history have significantly impacted the public health of human beings. The COVID-19 pandemic has further underscored the critical need for early detection and screening of infected individuals. However, current detection techniques are confronted with deficiencies in sensitivity and accuracy, restricting the capability of detecting trace amounts of viruses in human bodies and in the environments. The advent of DNA nanotechnology has opened up a feasible solution for rapid and sensitive virus determination. By harnessing the designability and addressability of DNA nanostructures, a range of rapid virus sensing platforms have been proposed. This review overviewed the recent progress, application, and prospect of DNA nanotechnology-based rapid virus detection platforms. Furthermore, the challenges and developmental prospects in this field were discussed.
RESUMO
Multiplexed profiling of RNAs aids in a comprehensive understanding of multiparameter-defined cellular processes and pathological states. We herein present a mass nanotags-enabled interfacial assembly system (MNTs-AS) with parallel amplification motors for simultaneous assaying of multiple RNAs in biosystems by matrix-assisted laser desorption/ionization mass spectrometry (MALDI MS). Four kinds of MNTs encoding corresponding RNA can be cyclically assembled on magnetic beads by target-triggered catalytic hairpin assembly (CHA) machineries on nanointerfaces, generating multiplexed and amplified characteristic ion signals assigned to target RNAs upon MALDI MS interrogation. By virtue of high sensitivity and multiplexing capability, the MNTs-AS-based MS assay allows precision subtyping of diverse breast cancer cells and their exosomes by multiplexed profiling of miRNA-21, miRNA-373, miRNA-155, and manganese superoxide dismutase mRNA via a single MS inquiry. This method provides a promising tool for unraveling multiple RNA-involved biological events in fundamental research and distinguishing different cancer subtypes in clinical practice.
Assuntos
MicroRNAs , RNA Mensageiro , MicroRNAs/genéticaRESUMO
Understanding of DNA-mediated charge transport (CT) is significant for exploring circuits at the molecular scale. However, the fabrication of robust DNA wires remains challenging due to the persistence length and natural flexibility of DNA molecules. Moreover, CT regulation in DNA wires often relies on predesigned sequences, which limit their application and scalability. Here, we addressed these issues by preparing self-assembled DNA nanowires with lengths of 30-120 nm using structural DNA nanotechnology. We employed these nanowires to plug individual gold nanoparticles into a circuit and measured the transport current in nanowires with an optical imaging technique. Contrary to the reported cases with shallow or no length dependence, a fair current attenuation was observed with increasing nanowire length, which experimentally confirmed the prediction of the incoherent hopping model. We also reported a mechanism for the reversible CT regulation in DNA nanowires, which involves dynamic transitions in the steric conformation.
Assuntos
Nanopartículas Metálicas , Nanofios , Nanofios/química , Ouro/química , Nanotecnologia/métodos , DNA/químicaRESUMO
Encoded nanostructures afford an ideal platform carrying multi-channel signal components for multiplexed assay and information security. However, with the demand on exclusivity and reproducibility of coding signals, precise control on the structure and composition of nanomaterials featuring fully distinguishable signals remains challenging. By using the multiplexing capability of mass spectrometry (MS) and spatial addressability of DNA origami nanostructures, we herein propose a quality control methodology for constructing mass-encoded nanodevices (namely MNTs-TDOFs) in the scaffold of compartmented tetrahedral DNA origami frames (TDOFs), in which the arrangement and stoichiometry of four types of mass nanotags (MNTs) can be finely regulated and customized to generate characteristic MS patterns. The programmability of combinatorial MNTs and orthogonality of individual compartments allows further evolution of MNTs-TDOFs to static tagging agents and dynamic nanoprobes for labeling and sensing of multiple targets. More importantly, structure control at single TDOF level ensures the constancy of prescribed MS outputs, by which a high-capacity coding system was established for secure information encryption and decryption. In addition to the multiplexed outputs in parallel, the nanodevices could also map logic circuits with interconnected complexity and logic events of c-Met recognition and dimerization on cell surface for signaling regulation by MS interrogation.
Assuntos
DNA , Nanoestruturas , Reprodutibilidade dos Testes , DNA/química , Nanoestruturas/química , Lógica , Nanotecnologia/métodosRESUMO
Delivery of CRISPR/Cas9 ribonucleoproteins (RNPs) offers a powerful tool for therapeutic genome editing. However, precise manipulation of CRISPR/Cas9 RNPs to switch the machinery on and off according to diverse disease microenvironments remains challenging. Here, we present dual-chain-locked DNA origami nanocages (DL-DONCs) that can confine Cas9 RNPs in the inner cavity for efficient cargo delivery and dual-marker-responsive genome editing in the specified pathological states. By engineering of ATP or miRNA-21-responsive dsDNAs as chain locks on the DONCs, the permeability of nanocages and accessibility of encapsulated Cas9 RNPs can be finely regulated. The resulting DL-DONCs enabled steric protection of bioactive Cas9 RNPs from premature release and deactivation during transportation while dismounting the dual chain locks in response to molecular triggers after internalization into tumor cells, facilitating the escape of Cas9 RNPs from the confinement for gene editing. Due to the dual-marker-dominated uncaging mechanism, the gene editing efficiency could be exclusively determined by the combined level of ATP and miRNA-21 in the target cellular environment. By targeting the tumor-associated PLK-1 gene, the DL-DONCs-enveloped Cas9 RNPs have demonstrated superior inhibitory effects on the proliferation of tumor cells in vitro and in vivo. The developed DL-DONCs provide a custom-made platform for the precise manipulation of Cas9 RNPs, which can be potentially applied to on-demand gene editing for classified therapy in response to arbitrary disease-associated biomolecules.
Assuntos
Sistemas CRISPR-Cas , MicroRNAs , Ribonucleoproteínas , DNA , Trifosfato de AdenosinaRESUMO
Self-assembly processes, while promising for enabling the fabrication of complexly organized nanomaterials from nanoparticles, are often limited in creating structures with multiscale order. These limitations are due to difficulties in practically realizing the assembly processes required to achieve such complex organizations. For a long time, a hierarchical assembly attracted interest as a potentially powerful approach. However, due to the experimental limitations, intermediate-level structures are often heterogeneous in composition and structure, which significantly impacts the formation of large-scale organizations. Here, we introduce a two-stage assembly strategy: DNA origami frames scaffold a coordination of nanoparticles into designed 3D nanoclusters, and then these clusters are assembled into ordered lattices whose types are determined by the clusters' valence. Through modulating the nanocluster architectures and intercluster bindings, we demonstrate the successful formation of complexly organized nanoparticle crystals. The presented two-stage assembly method provides a powerful fabrication strategy for creating nanoparticle superlattices with prescribed unit cells.
Assuntos
Nanopartículas , Nanoestruturas , DNA/química , Nanopartículas/química , Nanoestruturas/química , NanotecnologiaRESUMO
DNA nanomachines have been engineered into diverse personalized devices for diagnostic imaging of biomarkers; however, the regeneration of DNA nanomachines in living cells remains challenging. Here, we report an ingenious DNA nanomachine that can implement telomerase (TE)-activated regeneration in living cells. Upon apurinic/apyrimidinic endonuclease 1 (APE1)-responsive initiation of the nanomachine, the walker of the nanomachine moves along tracks regenerated by TE, generating multiply amplified signals through which APE1 can be imaged in situ. Additionally, augmentation of the signal due to the regeneration of the nanomachines could reveal differential expression of TE in different cell lines. To the best of our knowledge, this is the first proof-of-concept demonstration of the use of biomarkers to assist in the regeneration of nanomachines in living cells. This study offers a new paradigm for the development of more applicable and efficient DNA nanomachines.
Assuntos
Telomerase , Linhagem Celular , DNA/metabolismo , Regeneração , Telomerase/metabolismoRESUMO
Simultaneously monitoring and quantifying intracellular multiple microRNAs (miRNAs) is highly essential to clinical diagnosis and pathological research. However, revealing the intracellular distribution of multiple miRNAs while determining their content in a multiplex and quantitative format remains challenging. Considering the respective technical merit of fluorescence imaging and mass spectrometry (MS) in in situ detection and multiplex assaying, we herein propose fluorophore/mass dual-encoded nanoprobes (FMNPs) that can execute target-triggered hairpin self-assembly to enable in situ amplified imaging and follow-up MS quantification of intracellular multiple miRNAs. The FMNPs responsive to the target miRNA were constructed by codecorating gold nanoparticles (AuNPs) with locked hairpin DNA probes (LH1) and corresponding mass tags (MTs) for fluorescent and mass spectrometric dual-modal readout. Cellular miRNAs can separately trigger recycled hairpin self-assembly, leading to the continuous liberation of fluorophore-labeled bolt DNA (bDNA) for fluorescence imaging in cells. Moreover, the postreaction FMNPs afford an extra chance to validate the fluorescence output of miRNA-21 and miRNA-141 by accurate MS quantification relying on the ion signal of the barcoded MTs. Fluorescence imaging and MS quantification of miRNA-21 and miRNA-141 have also been successfully accomplished in different cell lines, highlighting its potential in cell subtyping. This "sense-and-validate" strategy creates a new modality for assaying multiple intracellular miRNAs and holds great promise in unveiling multicomponent-involved events in cellular processes and determining multiple biomarkers in accurate clinical diagnosis.
Assuntos
Nanopartículas Metálicas , MicroRNAs , Corantes Fluorescentes/química , Ouro/química , Ionóforos , Espectrometria de Massas , Nanopartículas Metálicas/química , MicroRNAs/análise , Imagem ÓpticaRESUMO
The dysfunctional islet ß-cell triggered by excessive deposition of Zn2+ constituted a striking indicator of the occurrence of diabetic disease. However, it remained a formidable challenge to reflect the real-time function of ß-cell by monitoring the Zn2+ content. Herein, multistage photoactivatable Zn2+-responsive nanodevice (denoted as AD2@USD1) was presented for sensing, regulating, and evaluating Zn2+ levels in dysfunctional islet ß-cells. The photoactivated signatures on the satellite shell layer of the nanodevices and the internally loaded chelating factors effectively identified and intervened in the real-time concentration of Zn2+, the photothermal feedback component decorated on the inner core permitted the assessment of the post-intervention Zn2+ levels, achieving an integrated intervention and prognostic assessment in response to the abnormal islet ß-cell function induced by Zn2+ deposition. In this way, one strategy for sensing and regulating islet ß-cell function-oriented to Zn2+ was established. Our study introduced AD2@USD1 as a tool for effectively sensing, adjusting, and assessing the Zn2+ level in islet ß-cells with abnormalities, gaining a potential breakthrough in the treatment of diabetes.
Assuntos
Diabetes Mellitus , Células Secretoras de Insulina , Ilhotas Pancreáticas , Quelantes , Humanos , ZincoRESUMO
Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) is widely applied in mapping macrobiomolecules in tissues, but it is still limited in profiling low-molecular-weight (MW) compounds (typically metabolites) due to ion interference and suppression by organic matrices. Here, we present a versatile "top-down" strategy for rational engineering of carbon material-based matrices, by which heteroatom-doped graphene quantum dots (HGQDs) were manufactured for LDI MS detection and imaging of small biomolecules. The HGQDs derived from parent materials inherited the π-conjugated networks and doping sites for promoting energy transfer and negative ion generation, while their extremely small size guaranteed the matrix uniformity and signal reproducibility in LDI MSI. Compared to other HGQDs, nitrogen-doped graphene quantum dots (NGQDs) exhibited superior capability of assisting LDI of various small molecules, including amino acids, fatty acids, saccharides, small peptides, nucleobases, anticancer drugs, and bisphenol pollutants. Density functional theory simulations also corroborated that the LDI efficiency was markedly raised by the proton-capturing pyridinic nitrogen species and compromised by the electron-deficient boron dopants. NGQDs-assisted LDI MS further enabled label-free investigation on enzyme kinetics using an ordinary short peptide as the substrate. Moreover, due to the high salt tolerance and signal reproducibility, the proposed negative-ion NGQDs-assisted LDI MSI was able to reveal the abundance and distribution of low-MW species in rat brain tissue and achieved the imaging of low-MW lipids in coronally sectioned rat brains subjected to traumatic brain injury. Our work offers a new route for customizing nanomaterial matrices toward LDI MSI of small biomolecules in biomedical and pathological research.
Assuntos
Grafite , Pontos Quânticos , Animais , Lasers , Nitrogênio , Peptídeos/análise , Ratos , Reprodutibilidade dos Testes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodosRESUMO
Proteins directly participate in tremendous physiological processes and mediate a variety of cellular functions. However, precise manipulation of proteins with predefined relative position and stoichiometry for understanding protein-protein interactions and guiding cellular behaviors is still challenging. With superior programmability of DNA molecules, DNA origami technology is able to construct arbitrary nanostructures that can accurately control the arrangement of proteins with various functionalities to solve these problems. Herein, starting from the classification of DNA origami nanostructures and the category of assembled proteins, we summarize the existing DNA origami-based protein manipulation systems (PMSs), review the advances on the regulation of their functions, and discuss their applications in cellular behavior modulation and disease therapy. Moreover, the limitations and potential directions of DNA origami-based PMSs are also presented, which may offer guidance for rational construction and ingenious application.
Assuntos
DNA , Nanoestruturas , DNA/química , Nanoestruturas/química , Nanotecnologia , Conformação de Ácido Nucleico , Proteínas/genéticaRESUMO
Although chemotherapy and photothermal therapy are widely used to combat cancer, their efficacy is often limited by multidrug resistance. Small interfering RNAs (siRNAs) have ability to suppress the expression of target genes, which has been extensively employed for combating the multidrug resistance to chemodrugs and hyperthermia in cancer therapy. However, efficient delivery of siRNAs along with chemo-photothermal agents in vivo is still an enormous challenge. Herein, octahedral DNA origami frameworks (OctDOFs) are constructed as a nanovehicle for precise organization and orchestrated delivery of siRNAs, chemodrugs (doxorubicin, Dox), and photothermal agents (gold nanorods, AuNRs) in combinatorial treatment of cancer. The inner cavity of the rigid OctDOFs structure is able to shield the encapsulated siRNAs during transportation by sterically hindering RNase degradation and protein binding, thus achieving effective downregulation of connective tissue growth factor (CTGF) and heat shock protein 72 (HSP72) for dual sensitization of cancer cells to chemodrugs and hyperthermia. By amplifying chemo-photothermal therapeutic potency with siRNAs, the proposed OctDOFs exhibited superior cytotoxicity and tumor inhibition efficacy in vitro and in vivo. This nanovehicle creates a promising siRNA delivery platform for precise medication and combination therapy.
Assuntos
Hipertermia Induzida , Fototerapia , Linhagem Celular Tumoral , DNA , Doxorrubicina , Terapia Fototérmica , RNA Interferente PequenoRESUMO
Mass spectrometry (MS) based analysis has received intense attention in diverse biological fields. However, direct MS interrogation of target biomolecules in complex biological samples is still challenging, due to the extremely low abundance and poor ionization potency of target biological species. Innovations in nanomaterials create new auxiliary tools for deep and comprehensive MS characterization of biomolecules. More recently, growing research interest has been directed to the compositional and structural engineering of nanomaterials for enriching target biomolecules prior to MS analysis, enhancing the ionization efficiency in MS detection and designing biosensing nanoprobes in sensitive MS readout. In this review, we mainly focus on the recent advances in the engineering of nanomaterials towards their applications in sample pre-treatment, desorption/ionization matrices and ion signal amplification for MS profiling of biomolecules. This review will provide a toolbox of nanomaterials for researchers devoted to developing analytical methods and practical applications in the biological MS field.
Assuntos
Nanoestruturas , Espectrometria de Massas , Manejo de Espécimes , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por MatrizRESUMO
Protein kinases constitute a rich pool of biomarkers and therapeutic targets of tremendous diseases including cancer. However, sensing kinase activity in vivo while implementing treatments according to kinase hyperactivation remains challenging. Herein, we present a nanomediator-effector cascade system that can in situ magnify the subtle events of kinase-catalyzed phosphorylation via DNA amplification machinery to achieve kinase activity imaging and kinase-responsive drug release in vivo. In this cascade, the phosphorylation-mediated disassembly of DNA/peptide complex on the nanomediators initiated the detachment of fluorescent hairpin DNAs from the nanoeffectors via hybridization chain reaction (HCR), leading to fluorescence recovery and therapeutic cargo release. We demonstrated that this nanosystem simultaneously enabled trace protein kinase A (PKA) activity imaging and on-demand drug delivery for inhibition of tumor cell growth both in vitro and in vivo, affording a kinase-specific sense-and-treat paradigm for cancer theranostics.
Assuntos
Antibióticos Antineoplásicos/farmacologia , DNA/química , Doxorrubicina/farmacologia , Nanopartículas/química , Técnicas de Amplificação de Ácido Nucleico , Peptídeos/química , Proteínas Quinases/metabolismo , Antibióticos Antineoplásicos/química , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , DNA/metabolismo , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Nanopartículas/metabolismo , Hibridização de Ácido Nucleico , Imagem Óptica , Peptídeos/metabolismo , Fosforilação , Proteínas Quinases/análiseRESUMO
Abnormal tumor microenvironment (TME) facilitates tumor proliferation and metastasis and establishes physiological barriers for effective transport of therapeutics inside the tumor, posing great challenges for cancer treatment. We designed a core-satellite size transformable nanoframework (denoted as T-PFRT) that can synchronously adapt to and remold TME for augmenting photodynamic therapy to inhibit tumor growth and prevent tumor metastasis. Upon matrix metalloproteinase 2 (MMP2)-responsive dissociation of the nanoframework in TME, the core structure loaded with TGFß signaling pathway inhibitor and oxygen-carrying hemoglobin aims to stroma remodeling and hypoxia relief, allowing photosensitizer-encapsulated satellite particles to penetrate to deep-seated tumor for oxygen-fueled photodynamic therapy. T-PFRT could overcome the stroma and hypoxia barriers for delivering therapeutics and gain excellent therapeutic outcomes in the treatment of primary and metastatic tumors.
Assuntos
Antineoplásicos/farmacologia , Nanopartículas/química , Fotoquimioterapia , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Hipóxia/tratamento farmacológico , Metaloproteinase 2 da Matriz/metabolismo , Estrutura Molecular , Tamanho da Partícula , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/química , Células Estromais/efeitos dos fármacos , Microambiente Tumoral/efeitos dos fármacosRESUMO
Upconversion nanoparticles (UCNPs) have potential applications in biosensing and bioimaging. However, the UCNPs-based sensors constructed by luminescence resonance energy transfer (LRET) always suffer from low quenching efficiency, hindering their application. Therefore, exploring a new strategy to resolve this issue is highly desirable. Herein, a strategy based on the surface plasmon resonance (SPR) effect of gold nanorods (AuNRs) is presented. The luminescence of UCNPs was modulated by adjusting the SiO2 thickness of AuNRs@SiO2 and the structure of UCNPs; an enhancement factor of ≈50 times was obtained. Based on the results of the SPR effect of AuNRs, we designed two kinds of potential upconversion microRNA sensors using microRNA-21 as a model to resolve the problem of the lower quenching efficiency resulting from a dye as a quencher. Studies revealed that the proposed strategy could be successfully used to construct upconversion microRNA sensors for avoiding the limitation of the low quenching efficiency. The sensitivity was ≈10â¯000 times higher than that of the upconversion sensor using dyes as quenchers. Importantly, the assay of microRNA-21 was successfully achieved using this sensor in human serum samples and human breast cancer cell (MCF-7) lysates. It provides a new method for designing upconversion microRNA sensors and may have potential for use in biosensing and bioimaging.
Assuntos
Ouro/química , MicroRNAs/metabolismo , Nanotubos/química , Humanos , LuminescênciaRESUMO
Due to the outstanding synergistic effects and low-toxicity, combination therapy exhibits more considerable potential in antitumor activity than monotherapy. Herein, a core-shell magnetic gold nanostar (Fe3O4@GNS, MGNS)-based system for codelivery of a mitochondrial targeting amphipathic tail-anchoring peptide (ATAP) and a membrane-associated cytokine (tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) was constructed. The magnetic core can facilitate delivery of the drug vehicle by external magnetic field, which results in accurate accumulation and enhances tumor cellular uptake for preliminary targeting. TRAIL and ATAP could sequentially target and be released toward the plasma membrane and mitochondria, initiating the extrinsic and intrinsic apoptosis pathways, respectively. The gold shell of MGNS can cause local tumor hyperthermia due to broad-band plasmon resonances in the near-infrared region, which can act as a complement with the peptide drug to further enhance apoptosis. Both in vitro and in vivo experiments revealed that rationally integrating extrinsic apoptosis, intrinsic apoptosis and hyperthermia for triplexed synergistic therapy, enabled the smart drug vehicle with pinpoint peptide drug delivery capabilities, and minimized side effects, enhancing the antitumor efficiency.