RESUMEN
Current chemodynamic therapy (CDT) primarily relies on the delivery of transition metal ions with Fenton activity to trigger hydroxyl radical production from hydrogen peroxide. However, administration of an excess amount of exogenous Fenton-type heavy metals may cause potential adverse effects to human health, including acute and chronic damages. Here, we present a new CDT strategy that uses intracellular labile iron pool (LIP) as the endogenous source of Fenton-reactive metals for eliciting free radical generation, and the discovery of hydroperoxides (R'OOH) as an optimal LIP-mediated chemodynamic agent against cancer. By simulating the metabolic fates of peroxo compounds within cells, R'OOH was found to have excellent free radical-producing ability in the presence of labile iron(II) and to suffer only moderate elimination by glutathione/glutathione peroxidase, which contributes to its superior chemodynamic efficacy. The LIP-initiated nontoxic-to-toxic transition of R'OOH, together with increased LIP levels in tumor cells, enabled efficient and specific CDT of cancer. Moreover, pH/labile iron(II) cascade-responsive nanomedicines comprising encapsulated methyl linoleate hydroperoxide and LIP-increasing agent in pH-sensitive polymer particles were fabricated to realize enhanced CDT. This work not only paves the way to using endogenous Fenton-type metals for cancer therapy but also offers a paradigm for the exploration of high-performance chemodynamic agents activated by intracellular LIP.
Asunto(s)
Antineoplásicos/farmacología , Neoplasias Encefálicas/terapia , Compuestos Ferrosos/metabolismo , Radicales Libres/metabolismo , Glioblastoma/terapia , Peróxidos/farmacología , Terapia Fototérmica , Antineoplásicos/química , Antineoplásicos/metabolismo , Neoplasias Encefálicas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Compuestos Ferrosos/química , Radicales Libres/química , Glioblastoma/patología , Humanos , Imagen Óptica , Peróxidos/química , Peróxidos/metabolismoRESUMEN
Chemodynamic therapy (CDT) employs Fenton catalysts to kill cancer cells by converting intracellular H2O2 into hydroxyl radical (â¢OH), but endogenous H2O2 is insufficient to achieve satisfactory anticancer efficacy. Despite tremendous efforts, engineering CDT agents with specific and efficient H2O2 self-supplying ability remains a great challenge. Here, we report the fabrication of copper peroxide (CP) nanodot, which is the first example of a Fenton-type metal peroxide nanomaterial, and its use as an activatable agent for enhanced CDT by self-supplying H2O2. The CP nanodots were prepared through coordination of H2O2 to Cu2+ with the aid of hydroxide ion, which could be reversed by acid treatment. After endocytosis into tumor cells, acidic environment of endo/lysosomes accelerated the dissociation of CP nanodots, allowing simultaneous release of Fenton catalytic Cu2+ and H2O2 accompanied by a Fenton-type reaction between them. The resulting â¢OH induced lysosomal membrane permeabilization through lipid peroxidation and thus caused cell death via a lysosome-associated pathway. In addition to pH-dependent â¢OH generation property, CP nanodots with small particle size showed high tumor accumulation after intravenous administration, which enabled effective tumor growth inhibition with minimal side effects in vivo. Our work not only provides the first paradigm for fabricating Fenton-type metal peroxide nanomaterials, but also presents a new strategy to improve CDT efficacy.
Asunto(s)
Antineoplásicos/uso terapéutico , Cobre/química , Peróxido de Hidrógeno/metabolismo , Neoplasias/tratamiento farmacológico , Puntos Cuánticos/uso terapéutico , Animales , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Humanos , Radical Hidroxilo/metabolismo , Lisosomas/efectos de los fármacos , Ratones , Puntos Cuánticos/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Herein, we report a nongenetic and real-time approach for imaging protein dimerization on living cell surfaces by aptamer recognition and proximity-induced DNA assembly. We use the aptamer specific for the receptor monomer as a recognition probe. When receptor dimerization occurs, the dimeric receptors bring two aptamer probes into close proximity, thereby triggering dynamic DNA assembly. The proposed approach was successfully applied to visualize dimerization of Met receptor and transforming growth factor-ß type II receptor. This approach allows us to image the two states (monomer/dimer) of a receptor protein on living cell surfaces in real time, opening a universal method for further investigation of protein dimerization and the corresponding activation processes in signal transduction.
Asunto(s)
Aptámeros de Nucleótidos/metabolismo , ADN/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Receptores de Factores de Crecimiento Transformadores beta/metabolismo , Aptámeros de Nucleótidos/química , Línea Celular Tumoral , ADN/química , Dimerización , Humanos , Microscopía Confocal , Proteínas Proto-Oncogénicas c-met/química , Receptores de Factores de Crecimiento Transformadores beta/química , Transducción de SeñalRESUMEN
The visualization of glycosylation states of specific proteins in vivo is of great importance for uncovering their roles in disease development. However, the ubiquity of glycosylation makes probing the glycans on a certain protein as difficult as looking for a needle in a haystack. Herein, we demonstrate a proximity-induced hybridization chain reaction (HCR) strategy for amplified visualization of protein-specific glycosylation. The strategy relies on designing two kinds of DNA probes, glycan conversion probes and protein recognition probes, which are attached to glycans and target proteins, respectively. Upon sequential binding to the targets, the proximity-induced hybridization between two probes occurs, which leads to the structure-switching of protein recognition probes, followed by triggering of HCR assembly. This strategy has been used to visualize tyrosine-protein kinase 7-specific sialic acid in living CEM cells and zebrafish and to monitor its variation during drug treatment. It provides a potential tool for investigating protein-specific glycosylation and researching the relation between dynamic glycans state and disease process.
Asunto(s)
Sondas de ADN/química , ADN/química , Glicoproteínas/análisis , Animales , Azidas/metabolismo , Carbocianinas/química , Línea Celular Tumoral , ADN/genética , Sondas de ADN/genética , Fluorescencia , Colorantes Fluorescentes/química , Glicoproteínas/química , Glicoproteínas/metabolismo , Glicosilación/efectos de los fármacos , Hexosaminas/metabolismo , Humanos , Microscopía Confocal , Microscopía Fluorescente , Hibridación de Ácido Nucleico , Polisacáridos/química , Tunicamicina/farmacología , Pez CebraRESUMEN
On cell-membrane surfaces, receptor-protein dimers play fundamental roles in many signaling pathways that are crucial for normal biological processes and cancer development. Efficient and sensitive analysis of receptor dimers in the native environment is highly desirable. Herein, we present a strategy for amplified imaging of receptor dimers in zebrafish and living cells that relies on aptamer recognition and proximity-induced hybridization chain reaction. Taking advantage of specific aptamer recognition and enzyme-free signal amplification, this strategy is successfully applied to the visualization of c-Met-receptor dimers in an HGF-independent or -dependent manner. Therefore, the developed imaging strategy paves the way for further investigation of the dimerization or oligomerization states of cell-surface receptors and their corresponding activation processes in zebrafish and living cells.
Asunto(s)
Aptámeros de Nucleótidos/metabolismo , Hibridación de Ácido Nucleico , Multimerización de Proteína , Receptores de Superficie Celular/química , Receptores de Superficie Celular/metabolismo , Proteínas de Pez Cebra/química , Proteínas de Pez Cebra/metabolismo , Animales , Línea Celular Tumoral , Supervivencia Celular , Humanos , Imagen Molecular , Estructura Cuaternaria de Proteína , Pez CebraRESUMEN
Autofluorescence background in complex biological samples is a major challenge in achieving high sensitivity of fluorescence immunoassays (FIA). Here we report an X-ray luminescence-based immunoassay for high-sensitivity detection of biomarkers using X-ray scintillating nanotags. Due to the weak scattering and absorption of most biological chromophores by X-ray excitation, a low-dose X-ray source can be used to produce intense scintillating luminescence from the nanotags for autofluorescence-free biosensing. To demonstrate this concept, we designed and synthesized NaGdF4:Tb@NaYF4 core/shell nanoparticles as kind of high-efficiency X-ray scintillating nanotags, which are able to convert high-energy X-ray photons to visible light without autofluorescence in biological samples. Notably, strong X-ray absorption and minimized surface quenching arising from the heavy Gd3+/Tb3+ atoms and core/shell architecture of the nanoparticles were found to be critically important for high-efficiency X-ray excited luminescence for high-sensitivity biosensing. Our method allows for sensing alpha-fetoprotein (AFP) biomarkers with a detection limit down to 0.25 ng/mL. Moreover, the as-described X-ray luminescence immunoassay exhibited an excellent biological specificity, high stability, and sample recovery, implying an opportunity for applications in complex biological samples. Consequently, our method can be readily extended for multiplexing sensing and medical diagnosis.
Asunto(s)
Inmunoensayo , Nanopartículas/química , Rayos X , alfa-Fetoproteínas/análisis , Animales , Biomarcadores/sangre , Células Cultivadas , Fluorescencia , Humanos , Inyecciones Subcutáneas , Mediciones Luminiscentes , Ratones , Ratones Desnudos , Nanopartículas/administración & dosificación , Neoplasias Experimentales/diagnóstico por imagen , Imagen Óptica , Tamaño de la Partícula , Propiedades de SuperficieRESUMEN
Black phosphorus (BP) nanomaterials have emerged as rapidly rising stars in the field of nanomedicine. In this work, BP quantum dots (BPQDs) are synthesized and their potential as photosensitizers is investigated for the first time. The BPQDs present good stability in physiological medium and no appreciable cytotoxicity. More importantly, the BPQDs can be rapidly eliminated from the body in their intact form via renal clearance due to their ultrasmall hydrodynamic diameter (5.4 nm). Both in vitro and in vivo studies indicate that the BPQDs have excellent photodynamic effect under light irradiation that can effectively generate reactive oxygen species to kill cancer cells. The BPQDs thus can serve as biocompatible and powerful photosensitizers for efficient photodynamic therapy.
Asunto(s)
Riñón/metabolismo , Fósforo/química , Fotoquimioterapia/métodos , Puntos Cuánticos/química , Puntos Cuánticos/metabolismo , Animales , Humanos , Fármacos Fotosensibilizantes/químicaRESUMEN
Optical manipulation appears to be a powerful tool for spatiotemporally controlling a variety of cellular functions. Herein, a photocontrolled DNA assembly approach is described which enables light-induced activation of cellular signal transduction by triggering protein dimerization (c-Met signalling in this case). Three kinds of DNA probes are designed, including a pair of receptor recognition probes with adaptors and a blocker probe with a photocleavable linker (PC-linker). By implementing PC-linkers in blocker probes, the designed DNA probes response to light irradiation, which then induces the assembly of receptor recognition probes through adaptor complementing. Consequently, light-mediated DNA assembly promotes the dimerization of c-Met receptors, resulting in activation of c-Met signalling. It is demonstrated that the proposed photocontrolled DNA assembly approach is effective for regulating c-Met signalling and modulating cellular behaviours, such as cell proliferation and migration. Therefore, this simple approach may offer a promising strategy to manipulate cell signalling pathways precisely in living cells.
Asunto(s)
Sondas de ADN/química , Proteínas Proto-Oncogénicas c-met/metabolismo , Aptámeros de Nucleótidos/química , Carbocianinas/química , Línea Celular Tumoral , Membrana Celular , Movimiento Celular , Proliferación Celular , Supervivencia Celular , Colorantes Fluorescentes/química , Humanos , Luz , Procesos Fotoquímicos , Multimerización de Proteína , Transducción de SeñalRESUMEN
A one-step reduction method was used for the preparation of stable graphitic carbon nitride-gold nanoparticles (g-C3N4-Au) nanocomposites from ultrathin g-C3N4 nanosheets and chloroauric acid by using NaBH4 as a reducing agent under ultrasonication. The nanocomposites were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, UV-Vis absorption and fluorescence spectroscopy etc. The results revealed that the gold nanoparticles (AuNPs) are uniformly formed on the g-C3N4 nanosheets. It is found that the peroxidase-like catalytic activity of this nanocomposite for the oxidation of 3,3',5,5'-tetramethylbenzidine by H2O2 to form a blue-colored product is strongly enhanced in the presence of Hg(II). Based on this phenomenon, a sensitive "turn-on" colorimetric assay for Hg(II) was developed that works at physiological pH values. Under optimal conditions, the absorption signal at 652 nm increases linearly with Hg(II) concentration in the range from 5 to 500 nM. A detection limit as low as 3.0 nM was achieved. This assay has excellent selectivity over other metal ions. It was successfully applied to the determination of Hg(II) in real water samples. The method is cost-effective, rapid, and allows for visual detection. Graphical abstract The nanocomposite composed of graphitic carbon nitride (g-C3N4) and gold nanoparticles (g-C3N4-AuNPs) can catalyze tetramethylbenzidine (TMB) oxidation by H2O2 to produce light-blue product (oxTMB). The peroxidase-like activity of g-C3N4-AuNPs can be greatly enhanced by Hg2+, thus increases the amount of the blue product formed.
Asunto(s)
Colorimetría/métodos , Oro , Mercurio/análisis , Nanocompuestos/química , Nanopartículas/química , Nitrilos/química , Colorimetría/normas , Grafito/química , Microscopía , Imitación Molecular , Peroxidasa , Análisis EspectralRESUMEN
Chemodynamic therapy (CDT) utilizes iron-initiated Fenton chemistry to destroy tumor cells by converting endogenous H2 O2 into the highly toxic hydroxyl radical (. OH). There is a paucity of Fenton-like metal-based CDT agents. Intracellular glutathione (GSH) with . OH scavenging ability greatly reduces CDT efficacy. A self-reinforcing CDT nanoagent based on MnO2 is reported that has both Fenton-like Mn2+ delivery and GSH depletion properties. In the presence of HCO3- , which is abundant in the physiological medium, Mn2+ exerts Fenton-like activity to generate . OH from H2 O2 . Upon uptake of MnO2 -coated mesoporous silica nanoparticles (MS@MnO2 NPs) by cancer cells, the MnO2 shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn2+ , resulting in GSH depletion-enhanced CDT. This, together with the GSH-activated MRI contrast effect and dissociation of MnO2 , allows MS@MnO2 NPs to achieve MRI-monitored chemo-chemodynamic combination therapy.
Asunto(s)
Antineoplásicos/farmacología , Glutatión/química , Compuestos de Manganeso/farmacología , Nanopartículas/química , Óxidos/farmacología , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Iones/química , Compuestos de Manganeso/administración & dosificación , Compuestos de Manganeso/química , Ratones , Nanopartículas/administración & dosificación , Neoplasias Experimentales/tratamiento farmacológico , Neoplasias Experimentales/patología , Óxidos/administración & dosificación , Óxidos/química , Tamaño de la Partícula , Relación Estructura-Actividad , Propiedades de SuperficieRESUMEN
The development of functional DNA-based nanosensors in living cells has experienced some design challenges, including, for example, poor cellular uptake, rapid nuclease degradation, and high false positives. Herein, we designed selectively permeable poly(methacrylic acid) (PMA) nanocapsules to encapsulate functional DNAs for metal ions and small-molecules sensing in living cells. Since functional DNAs are concentrated in the nanocapsules, an increasing reaction rate is obtained in vitro. During endocytosis, polymeric capsules simultaneously improve cellular uptake of functional DNAs and preserve their structural integrity inside the confined capsule space. More importantly, selective shell permeability allows for the free diffusion of small molecular targets through capsule shells but limits the diffusion of large biomolecules, such as nuclease and nonspecific protein. Compared to the free DNAzyme, PMA nanocapsules could reduce false positives and enhance detection accuracy. Furthermore, PMA nanocapsules are biocompatible and biodegradable. Through the controllability of wall thickness, permeability, and size distribution, these nanocapsules could be expanded easily to other targets, such as microRNAs, small peptides, and metabolites. These nanocapsules will pave the way for in situ monitoring of various biological processes in living cells and in vivo.
Asunto(s)
Técnicas Biosensibles/métodos , ADN/química , Nanocápsulas/química , Zinc/metabolismo , Reactores Biológicos , Carbocianinas/química , ADN Catalítico/metabolismo , Humanos , Plomo/química , Plomo/metabolismo , Membrana Dobles de Lípidos/química , Células MCF-7 , Microscopía Confocal , Tamaño de la Partícula , Ácidos Polimetacrílicos/química , Dióxido de Silicio/química , Espectrometría de Fluorescencia , Zinc/químicaRESUMEN
Smart assemblies have attracted increased interest in various areas, especially in developing novel stimuli-responsive theranostics. Herein, commercially available, natural tannic acid (TA) and iron oxide nanoparticles (Fe3 O4 NPs) are utilized as models to construct smart magnetic assemblies based on polyphenol-inspired NPs-phenolic self-assembly between NPs and TA. Interestingly, the magnetic assemblies can be specially disassembled by adenosine triphosphate, which shows a stronger affinity to Fe3 O4 NPs than that of TA and partly replaces the surface coordinated TA. The disassembly can further be facilitated by the acidic environment hence causing the remarkable change of the transverse relaxivity and potent "turn-on" of fluorescence (FL) signals. Therefore, the assemblies for specific and sensitive tumor magnetic resonance and FL dual-modal imaging and photothermal therapy after intravenous injection of the assemblies are successfully employed. This work not only provides understandings on the self-assembly between NPs and polyphenols, but also will open new insights for facilely constructing versatile assemblies and extending their biomedical applications.
Asunto(s)
Adenosina Trifosfato/química , Hipertermia Inducida , Imagen por Resonancia Magnética , Neoplasias/terapia , Imagen Óptica , Fototerapia , Polifenoles/fisiología , Animales , Dispersión Dinámica de Luz , Fluorescencia , Células Hep G2 , Humanos , Concentración de Iones de Hidrógeno , Rayos Infrarrojos , Ratones , Neoplasias/patología , SolucionesRESUMEN
Hydrogels are crosslinked hydrophilic polymers that can absorb a large amount of water. By their hydrophilic, biocompatible and highly tunable nature, hydrogels can be tailored for applications in bioanalysis and biomedicine. Of particular interest are DNA-based hydrogels owing to the unique features of nucleic acids. Since the discovery of the DNA double helical structure, interest in DNA has expanded beyond its genetic role to applications in nanotechnology and materials science. In particular, DNA-based hydrogels present such remarkable features as stability, flexibility, precise programmability, stimuli-responsive DNA conformations, facile synthesis and modification. Moreover, functional nucleic acids (FNAs) have allowed the construction of hydrogels based on aptamers, DNAzymes, i-motif nanostructures, siRNAs and CpG oligodeoxynucleotides to provide additional molecular recognition, catalytic activities and therapeutic potential, making them key players in biological analysis and biomedical applications. To date, a variety of applications have been demonstrated with FNA-based hydrogels, including biosensing, environmental analysis, controlled drug release, cell adhesion and targeted cancer therapy. In this review, we focus on advances in the development of FNA-based hydrogels, which have fully incorporated both the unique features of FNAs and DNA-based hydrogels. We first introduce different strategies for constructing DNA-based hydrogels. Subsequently, various types of FNAs and the most recent developments of FNA-based hydrogels for bioanalytical and biomedical applications are described with some selected examples. Finally, the review provides an insight into the remaining challenges and future perspectives of FNA-based hydrogels.
Asunto(s)
Investigación Biomédica , Técnicas Biosensibles , ADN/química , Hidrogeles/química , Animales , HumanosRESUMEN
In this work, uniformly-dispersed platinum nanoparticles (PtNPs) were synthesized by a simple chemical reduction method, in which citric acid and sodium borohydride acted as a stabilizer and reducer, respectively. An ultrasensitive colorimetric sensor for the facile and rapid detection of Ag⺠ions was constructed based on the peroxidase mimetic activities of the obtained PtNPs, which can catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to produce colored products. The introduced Ag⺠would be reduced to Ag° by the capped citric acid, and the deposition of Ag° on the PtNPs surface, can effectively inhibit the peroxidase-mimetic activity of PtNPs. Through measuring the maximum absorption signal of oxidized TMB at 652 nm, ultra-low detection limits (7.8 pM) of Ag⺠can be reached. In addition to such high sensitivity, the colorimetric assay also displays excellent selectivity for other ions of interest and shows great potential for the detection of Ag⺠in real water samples.
RESUMEN
An ultrasensitive and specific electrochemiluminescence (ECL) biosensor has been designed for the p53 DNA sequence, which is based on cascade signal amplification of nicking endonuclease assisted target recycling and hyperbranched rolling circle amplification (HRCA). First of all, biotin modified hairpin capture DNA (HP) probe was immobilized on the surface of streptavidin magnespheres paramagnetic particles (PMPs). Target DNA hybridized with the loop portion of the HP probe, therefore unfolding HP to form a double-stranded DNA (dsDNA) containing the specific nicking site of the nicking endonuclease. Then, the nicking endonuclease recognized the specific nicking site and cleaved the HP into two pieces, liberating target DNA and the complementary sequence piece for the padlock probe. The intact target DNA would initiate the next cycle of hybridization and cleavage, thereby releasing multiple complementary sequences for the padlock probes. The liberated complementary sequences hybridized with the padlock probes, subsequently inducing the HRCA reaction and generating numerous dsDNA segments. Herein, Ru(phen)3(2+) was embedded into dsDNA and worked as ECL signal reporter. The reaction products were eventually pretreated by dialysis tube with the cutoff membrane to remove the residual Ru(phen)3(2+) in the solution for the following ECL measurements. Using this cascade amplification strategy, an ultrasensitive p53 DNA sequence detection method was developed with a wide linear range from 0.05 to 100 fM and a low detection limit of 0.02 fM. Moreover, this cascade amplified ECL biosensor had specific recognition capacity for noncomplementary and single- and double-base mismatched DNA. The proposed ECL biosensor might have a great potential in biomedical research and clinic analysis.
Asunto(s)
Técnicas Biosensibles/métodos , ADN/sangre , Técnicas de Amplificación de Ácido Nucleico/métodos , Proteína p53 Supresora de Tumor/genética , Secuencia de Bases , ADN/genética , Sondas de ADN/química , Sondas de ADN/genética , Técnicas Electroquímicas/métodos , Endonucleasas/química , Humanos , Límite de Detección , Mediciones LuminiscentesRESUMEN
Graphitic carbon nitrides (g-C3 N4 ) are a class of 2D polymeric materials mainly composed of carbon and nitrogen atoms. g-C3 N4 are attracting dramatically increasing interest in the areas of sensing, imaging, and therapy, due to their unique optical and electronic properties. Here, the luminescent properties (mainly includes photoluminescence and electrochemiluminescence), and catalytic and photoelectronic properties related to sensing and therapy applications of g-C3 N4 materials are reviewed. Furthermore, the fabrication and advantages of sensing, imaging and therapy systems based on g-C3 N4 materials are summarized. Finally, the future perspectives for developing the sensing, imaging and therapy applications of the g-C3 N4 materials are discussed.
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Técnicas Biosensibles , Diagnóstico por Imagen , Grafito/uso terapéutico , Nitrilos/química , Catálisis , Grafito/química , LuminiscenciaRESUMEN
Theranostic nanomedicines that integrate diagnostic and therapeutic moieties into a single nanoscale platform are playing an increasingly important role in fighting cancer. Here, a facile and green synthetic strategy for hollow CoPt alloy nanoparticles (HCPA-NPs) using plant polyphenols as assisted agents is reported for the first time. This novel strategy enables size-controlled synthesis of HCPA-NPs through the control of the molecular sizes of polyphenols. It is also a versatile strategy for synthesizing other hollow alloy nanoparticles with various metal compositions due to the diverse metal-chelating ability of the polyphenols. Further studies show that HCPA-NPs have good biocompatibility and can be successfully implemented for magnetic resonance and photoacoustic dual-modal imaging guided photothermal therapy. This work brings new insights for the green synthesis of hollow nanoparticles and extends these biocompatible nanoparticles for theranostic applications.
Asunto(s)
Aleaciones/química , Tecnología Química Verde/métodos , Hipertermia Inducida , Nanopartículas del Metal/química , Imagen Multimodal , Fototerapia , Polifenoles/química , Animales , Supervivencia Celular , Células HeLa , Células Hep G2 , Humanos , Células MCF-7 , Imagen por Resonancia Magnética , Nanopartículas del Metal/ultraestructura , Ratones , Polietilenglicoles/química , Taninos/químicaRESUMEN
Metal nanoclusters (NCs) are emerging as a new class of functional nanomaterials in the area of biological sensing, labelling, imaging and therapy due to their unique physical and chemical properties, such as ultrasmall size, HOMO-LUMO transition, strong luminescence together with good photostability and biocompatibility. A recent surge of interest in this field is the surface functionalization of these metal NCs through which one can tailor their physicochemical properties, such as stability in solution, and strong luminescence, as well as their biodistribution and toxicity in biological systems, which in turn can empower these functionalized NCs with desirable targeting, imaging, and therapeutic ability for biomedical applications. In this review, we first introduce the functionalization strategies for the metal NCs developed in the past few years, followed by highlighting some biomedical applications of these functionalized metal NCs. We then discuss the difference of in vitro and in vivo fate as well as toxicity between various functionalized metal NCs. Finally, we present a short discussion on the current challenges and provide an outlook of the future developments of these functional metal NCs.
Asunto(s)
Nanopartículas del Metal/química , Animales , Diagnóstico por Imagen , Portadores de Fármacos , Humanos , Luminiscencia , Fotoquimioterapia , Radioterapia , Distribución TisularRESUMEN
Hydrophobic nanoparticles have shown substantial potential for bioanalysis and biomedical applications. However, their use is hindered by complex phase transfer and inefficient surface modification. This paper reports a facile and universal strategy for phase transfer and surface biofunctionalization of hydrophobic nanomaterials using aptamer-pendant DNA tetrahedron nanostructures (Apt-tet). The Janus DNA tetrahedron nanostructures are constructed by three carboxyl group modified DNA strands and one aptamer sequence. The pendant linear sequence is an aptamer, in this case AS1411, known to specifically bind nucleolin, typically overexpressed on the plasma membranes of tumor cells. The incorporation of the aptamers adds targeting ability and also enhances intracellular uptake. Phase-transfer efficiency using Apt-tet is much higher than that achieved using single-stranded DNA. In addition, the DNA tetrahedron nanostructures can be programmed to permit the incorporation of other functional nucleic acids, such as DNAzymes, siRNA, or antisense DNA, allowing, in turn, the construction of promising theranostic nanoagents for bioanalysis and biomedical applications. Given these unique features, we believe that our strategy of surface modification and functionalization may become a new paradigm in phase-transfer-agent design and further expand biomedical applications of hydrophobic nanomaterials.
Asunto(s)
ADN/química , Interacciones Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Modelos Moleculares , Conformación de Ácido Nucleico , Propiedades de SuperficieRESUMEN
Here, we report the synthesis and characterization of size-controllable and stimuli-responsive DNA nanohydrogels as effective targeted gene delivery vectors. DNA nanohydrogels were created through a self-assembly process using three kinds of building units, respectively termed Y-shaped monomer A with three sticky ends (YMA), Y-shaped monomer B with one sticky end (YMB), and DNA linker (LK) with two sticky ends. Hybridization at the sticky ends of monomers and LK leads to nanohydrogel formation. DNA nanohydrogels are size-controllable by varying the ratio of YMA to YMB. By incorporating different functional elements, such as aptamers, disulfide linkages, and therapeutic genes into different building units, the synthesized aptamer-based nanohydrogels (Y-gel-Apt) can be used for targeted and stimuli-responsive gene therapy. Y-gel-Apt strongly inhibited cell proliferation and migration in target A549 cells, but not in control cells. By taking advantage of facile modular design and assembly, efficient cellular uptake, and superior biocompatibility, this Y-gel-Apt holds great promise as a candidate for targeted gene or drug delivery and cancer therapy.