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1.
Anal Chim Acta ; 1112: 24-33, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32334679

RESUMO

Multiplex detection of microRNAs is highly desirable in trace analysis of clinical samples for early-stage disease diagnosis. In the present study, we report a new liquid suspension nano-chip technology for multiplex detection of microRNAs by detecting side scatter and fluorescence signals of molecular beacon-modified polystyrene nanoparticles, simultaneously. Polystyrene nanoparticles were encoded by distinguished intensity of scattered light with tunable sizes (120 nm, 200 nm and 280 nm). In the proposed detection system, the fluorescence of 5-carboxyfluorescein was recovered due to the structure change of molecular beacons from hairpin to rod-like shape caused by the hybridization of target microRNAs. The well-designed liquid suspension nano-chip system enabled quantitative detection of three colorectal cancer-related microRNAs with low limits of detection and high sensitivity. More importantly, for simulated clinical samples, three random mixed microRNAs were simultaneously detected by accurately decoding the scattering intensity of polystyrene nanoparticles of different sizes and quantitatively analyzed by fluorescence intensity. This technology provides a washing-free, sensitive, convenient and small loading volume strategy for detecting clinical multiplex nucleic acid samples.

2.
Nanoscale ; 12(15): 8248-8254, 2020 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-32239032

RESUMO

Probes functioning in the second near-infrared window (1000-1700 nm, NIR-II) exhibit higher resolution and diminished auto-fluorescence compared to those in the traditional NIR region (700-950 nm). Here, we designed and synthesized rare earth ion doped probes with core/shell/shell structures and bright luminescence in the NIR-II region excited at 808 nm. With the doping of Ce3+ ions, the emission intensity of Er3+ at 1530 nm increased 10 times, while the upconversion luminescence decreased to less than 1%. After being modified with polyacrylic acid and polyethylene glycol, the as-obtained water-soluble probe exhibits continuous high-resolution for distinguishing 0.25 mm blood vessels even 10 h after injection. Noteworthily, the imaging of tumors was achieved by injecting the probe, indicating that the designed NIR-II probe has sufficient brightness and the ability to passively target tumor tissue.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32329996

RESUMO

Fluorescence sensing exhibits advantages of real-time, non-invasive, convenient, and less impact on the original environment for in vivo detection. Here a reversible time-gated ratiometric in vivo detection method that could eliminate the interferences from probe amount, photon scattering and absorption is proposed. Correspondingly, the composite probe must be able to reversibly respond to changes in the microenvironment and emit two luminescent signals at the same working wavelength, but different lifetimes. Benefitting from the reversible detection mechanism, the probes could be used to monitor a dynamic biological process and the ratio signal value could be determined only by the concentration of analytes but independent of the probe concentration. And benefitting from the same working wavelength, the read-out errors from photon absorption and scattering could be minimized. This method is very suitable for in vivo detection in which the probe distribution and depth is unknown and variable. As a typical model, the different pH values in the gastrointestinal area and pH changes caused by drugs and fasting are successfully monitored.

4.
Theranostics ; 10(7): 3281-3292, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194868

RESUMO

Hormone therapy (HT) is one of the most effective treatments for osteoporosis. However, the nonselective accumulation of hormone in organs such as breast, heart and uterus other than bones causes serious side effects, which impedes the application of HT. Hence, it is critically important to develop a HT strategy with reduced non-specific enrichment of hormone drugs in non-target tissues and enhanced bone-targeting ability. Methods: Herein, a 17ß-estradiol (E2)-laden mesoporous silica-coated upconversion nanoparticle with a surface modification of ethylenediaminetetraacetic acid (EDTA) (NaLuF4:Yb,Tm@NaLuF4@mSiO2-EDTA-E2, E2-csUCNP@MSN-EDTA) is developed for bone-targeted osteoporosis hormone therapy. EDTA was attached onto the surface of E2 upconversion nanocomposite to enhance its affinity and efficiency targeting bone tissue and cells to optimize hormone replacement therapy for osteoporosis. We characterized the size, cytotoxicity, loading and release efficiency, in situ and ex vivo imaging. Further, in vitro and in vivo osteogenic ability was tested using preosteoblast and ovariectomy mouse model of osteoporosis. Results: The upconversion core of E2-csUCNP@MSN-EDTA nanoparticle serves as an excellent imaging agent for tracking the loaded hormone drug in vivo. The mesoporous silica layer has a high loading efficiency for E2 and provides a relatively long-lasting drug release within 50 h. EDTA anchored on the silica layer endows the nanocomposite with a bone targeting property. The nanocomposite effectively reverses estrogen deficiency-induced osteoporosis and reduces the damage of hormone to the uterus. The bone mineral density in the nanocomposite treatment group is nearly twice that of the ovariectomized (OVX) group. Compared with the E2 group, the uterine weight and luminal epithelial height were significantly lower in the nanocomposite treatment group. Conclusion: This work demonstrated that E2-csUCNP@MSN-EDTA alleviates the side effect of hormone therapy while maintaining its therapeutic efficacy, which has great potential for developing the next generation of methods for osteoporosis treatment.

5.
Nanoscale ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32068223

RESUMO

Fabricating lanthanide doped up-conversion luminescence based nanocomposites has drawn increasing attention in nanoscience and nanotechnology. Although challenging in precise synthesis, structure manipulation and interfacial engineering, fabricating dendritic mesoporous silica coated up-conversion nanoparticles (UCNP@dMSNs) with a tunable pore size is of great importance for the functionalization and application of UCNPs. Herein, we report a strategy to prepare uniform monodisperse UCNP@dMSNs with a core-shell structure. The silica shell has tunable center-radial and dendritic mesoporous channels. The synthesis was carried out in the heterogeneous oil-water microemulsion phase of the Winsor III system reaction system, which allows silica to be deposited directly on hydrophobic UCNPs through the self-anchoring of micelle complexes on the oleic acid ligand. The average pore size of UCNP@dMSNs could be tailored from ∼10 to ∼35 nm according to the varied amounts of co-solvent in the mixture. The microemulsion approach could also be used to prepare hierarchical UCNP@dMSNs with a multi-generational mesostructure. The resultant UCNP@dMSNs exhibit the unique advantage of loading "guest" nanoparticles in a self-absorption manner. We proved that Cu1.8S NPs (∼10 nm), Au NPs (∼10 nm) and Fe3O4 NPs (∼25 nm) could be incorporated in UCNP@dMSNs, which in turn validates the high adsorption capacity of UCNP@dMSNs.

6.
J Mater Chem B ; 8(12): 2410-2417, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32100811

RESUMO

Gemcitabine (GEM) has been the recommended first-line drug for patients with pancreatic ductal adenocarcinoma cancer (PDAC) for the last twenty years. However, GEM-based treatment has failed in many patients because of the drug resistance acquired during tumorigenesis and development. To override resistance to GEM in pancreatic cancer, we developed a visualisable, photothermally controlled, drug release nanosystem (VPNS). This nanosystem has NaLuF4:Nd@NaLuF4 nanoparticles as the luminescent core, octabutoxyphthalocyanine palladium(ii) (PdPc) as the photothermal agent, and phosphorylated gemcitabine (pGEM) as the chemodrug. pGEM, one of the active forms of GEM, can circumvent the insufficient activation of GEM in cancer cell metabolism. The NaLuF4:Nd@NaLuF4 nanoparticles were employed to visualise the tumor lesion in vivo by their near-infrared luminescence. The near-infrared light-triggered photothermal effect from PdPc could trigger the release of pGEM loaded in a thermally responsive ligand and simultaneously enable photothermal cancer treatment. This work presents an effective method that suppresses the growth of tumour cells with dual-mode treatment and enables the improved treatment of orthotopic nude mice afflicted with pancreatic cancer.

7.
ACS Appl Mater Interfaces ; 12(4): 4358-4365, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31904925

RESUMO

The lateral flow immunoassay test (LFT), as a method of a point of care test, is widely used in disease diagnosis, food security, and environment observation due to its portability and testing rapidity. A fluorescence lateral flow immunoassay was developed recently to enhance the sensitivity and accuracy of the LFT. However, for most fluorescence reporters, their emission and excitation wavelengths are located in the ultraviolet or visible region. Serum or whole blood significantly absorbs and scatters light of this region, and this will result in background signal interference. In this study, we replace traditional fluorescence reporters with near-infrared lanthanide-doped nanoparticles (NIR-RENPs) to establish a NIR-LFT platform. Blood and other biological samples scatter and absorb less near-infrared light than visible light, and the autofluorescence of biological samples is rarely located in this region. Therefore, using NIR light as a signal can diminish the interference of background noise and suffer from less signal attenuation. In addition, compared with commonly used NIR organic dye, NIR-RENPs have better stability. It is promising that lateral flow immunoassays based on NIR lanthanide-doped nanoparticles are able to acquire a lower detection limit and better accuracy, and they are more suitable for application in commercial settings.

8.
Nat Commun ; 11(1): 4, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911593

RESUMO

The in vivo temperature monitoring of a microenvironment is significant in biology and nanomedicine research. Luminescent nanothermometry provides a noninvasive method of detecting the temperature in vivo with high sensitivity and high response speed. However, absorption and scattering in complex tissues limit the signal penetration depth and cause errors due to variation at different locations in vivo. In order to minimize these errors and monitor temperature in vivo, in the present work, we provided a strategy to fabricate a same-wavelength dual emission ratiometric upconversion luminescence nanothermometer based on a hybrid structure composed of upconversion emissive PbS quantum dots and Tm-doped upconversion nanoparticles. The ratiometric signal composed of two upconversion emissions working at the same wavelength, but different luminescent lifetimes, were decoded via a time-resolved technique. This nanothermometer improved the temperature monitoring ability and a thermal resolution and sensitivity of ~0.5 K and ~5.6% K-1 were obtained in vivo, respectively.


Assuntos
Termometria/instrumentação , Chumbo/química , Luminescência , Nanopartículas/química , Pontos Quânticos/química , Temperatura , Termometria/métodos
9.
Angew Chem Int Ed Engl ; 59(7): 2628-2633, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31793153

RESUMO

Deepening our understanding of mammalian gut microbiota has been greatly hampered by the lack of a facile, real-time, and in vivo bacterial imaging method. To address this unmet need in microbial visualization, we herein report the development of a second near-infrared (NIR-II)-based method for in vivo imaging of gut bacteria. Using d-propargylglycine in gavage and then click reaction with an azide-containing NIR-II dye, gut microbiota of a donor mouse was strongly labeled with NIR-II fluorescence on their peptidoglycan. The bacteria could be readily visualized in recipient mouse gut with high spatial resolution and deep tissue penetration under NIR irradiation. The NIR-II-based metabolic labeling strategy reported herein, provides, to the best of our knowledge, the first protocol for facile in vivo visualization of gut microbiota within deep tissues, and offers an instrumental tool for deciphering the complex biology of these gut "dark matters".

10.
Anal Chem ; 92(2): 2027-2033, 2020 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-31875673

RESUMO

Near-infrared luminescent emission has been widely used as a signal for biological detection with its high spatial resolution and fast response. Rare-earthdoped nanoparticle-dye composites have diverse advantages of a wide operation wavelength and remarkable light stability, while the application is limited by the low luminescence quantum yield of rare-earth nanoparticles. Hence, in this work, we use a singly Yb doped nanoparticle that has strong luminescence emission at 975 nm under excitation at the same wavelength as an energy donor to construct the detection system. An inner filter pair, composed of core-shell nanophosphor NaYF4/20%Yb@NaYF4 (1:2) nanocrystals (csYb) as a luminescent beacon and ClO--responsive cyanine dye Cy890 as a filtering agent, was designed as a model. With a time-gated detection mode, the nanocomposites realize the detection limit at 0.55 ppb as demonstrated in a ClO- detection trial. The csYb&Cy890 nanocomposites can also monitor ClO- by luminescence signals in both living cells and mice models.

11.
Inorg Chem ; 58(21): 14490-14497, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31600068

RESUMO

In this paper, we utilized the energy-transfer process between upconversion nanoparticles (UCNPs) and organic dye molecules to enhance the upconversion quantum yield (UCQY) of a UCNPs-dye system and tune the luminescence output color. The results indicate that adding an energy dissipation pathway to the energy donor through an energy-transfer process can decrease the ratio of nonradiative transition and cause a new radiative pathway. Through calculation of the rate equations, we studied the effects of the energy-transfer efficiency and activator type on the UCQY enhancement. On the basis of calculations of the CIE color coordinates, tunable color from Er3+, Tm3+, Ho3+, and Tb3+ ions was generated by surface decorating of an organic dye. The approach described here provides a new way to optimize the UCQY and manipulate the emission through energy transfer in a nanoscopic region.

12.
Angew Chem Int Ed Engl ; 58(52): 18793-18797, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31565827

RESUMO

Sactionine-containing antibiotics (sactibiotics) are a growing class of peptide antibiotics belonging to the ribosomally synthesized and post-translationally modified peptide (RiPP) superfamily. We report the characterization of thuricin Z, a novel sactibiotic from Bacillus thuringiensis. Unusually, the biosynthesis of thuricin Z involves two radical S-adenosylmethionine (SAM) enzymes, ThzC and ThzD. Although ThzC and ThzD are highly divergent from each other, these two enzymes produced the same sactionine ring in the precursor peptide ThzA in vitro. Thuricin Z exhibits narrow-spectrum antibacterial activity against Bacillus cereus. A series of analyses, including confocal laser scanning microscopy, ultrathin-sectioning transmission electron microscopy, scanning electron microscopy, and large-unilamellar-vesicle-based fluorescence analysis, suggested that thuricin Z binds to the bacterial cell membrane and leads to membrane permeabilization.

13.
Small ; 15(46): e1904487, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31565853

RESUMO

For years, luminescence lifetime imaging has served as a quantitative tool in indicating intracellular components and activities. However, very few studies involve the in vivo study of animals, especially in vivo stimuli-responsive activities of animals, as both excitation and emission wavelengths should fall into the near-infrared (NIR) optical transparent window (660-950 and 1000-1500 nm). Herein, this work reports a lifetime-responsive nanocomposite with both excitation and emission in the NIR I window (800 nm) and lifetime in the microsecond region. The incorporation of Tm3+ -doped rare-earth nanocrystals and NIR dye builds an efficient energy transfer pathway that enables a tunable luminescence lifetime range. The NaYF4 :Tm nanocrystal, which absorbs and emits photons at the same energy level, is found to be 33 times brighter than optimized core-shell upconversion nanocrystals, and proved to be an effective donor for NIR luminescence resonance energy transfer (LRET). The anti-interference capability of luminescence lifetime signals is further confirmed by luminescence and lifetime imaging. In vivo studies also verify the lifetime response upon stimulation generated in an arthritis mouse model. This work introduces an intriguing tool for luminescence lifetime-based sensing in the microsecond region.

14.
Theranostics ; 9(16): 4597-4607, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31367243

RESUMO

During a minimally invasive tumor resection procedure, it is still a challenge to rapidly and accurately trace tiny malignant tumors in real time. Fluorescent molecular imaging is considered an efficient method of localizing tumors during surgery due to its high sensitivity and biosafety. On the basis of the fact that γ-glutamyltranspeptidase (GGT) is overexpressed in ovarian cancer, we herein designed a highly sensitive ratiometric fluorescent GGT-responsive probe Py-GSH for rapid tumor detection. Methods: The GGT response probe (Py-GSH) was constructed by using GSH group as a response group and pyrionin B as a fluorescent reporter. Py-GSH was characterized for photophysical properties, response speed and selectivity of GGT and response mechanism. The anti-interference ability of ratiometric probe Py-GSH to probe concentration and excitation power was evaluated both in vitro and in tissue. The biocompatibility and toxicity of the ratiometric probe was examined using cytoxicity test. The GGT levels in different lines of cells were determined by ratiometric fluorescence imaging and cytometry analysis. Results: The obtained probe capable to rapidly monitored GGT activity in aqueous solution with 170-fold ratio change. By ratiometric fluorescence imaging, the probe Py-GSH was also successfully used to detect high GGT activity in solid tumor tissues and small peritoneal metastatic tumors (~1 mm in diameter) in a mouse model. In particular, this probe was further used to determine whether the tissue margin following clinical ovarian cancer surgery contained tumor. Conclusion: In combination of ratiometric fluorescence probes with imaging instrument, a point-of-care imaging method was developed and may be used for surgical navigation and rapid diagnosis of tumor tissue during clinical tumor resection.

15.
Inorg Chem ; 58(14): 9351-9357, 2019 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-31246450

RESUMO

We designed and synthesized NaYF4:Yb,Tm@LiLuF4:Nd core-shell nanoparticles, which can emit at ∼800 nm under 980 nm excitation and at ∼1060 nm under 808 nm excitation, simultaneously having an upconversion and downshifting mechanism for near-infrared (NIR) emission. After surface modification with sodium citrate, the soluble nanoparticles were used in the in vitro NIR luminescence imaging to compare the penetration depth and the scattering of tissue. Furthermore, to determine the differences between the upconversion and downshifting fluorescence for biological imaging, the soluble nanoparticles also were operated on the aforementioned two modes for in vivo imaging.


Assuntos
Diagnóstico por Imagem/métodos , Elementos da Série dos Lantanídeos/química , Nanopartículas Metálicas/química , Animais , Luminescência , Camundongos , Espectroscopia de Luz Próxima ao Infravermelho
16.
Chem Sci ; 10(15): 4227-4235, 2019 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-31057751

RESUMO

Time-resolved fluorescence lifetime imaging (FLIM) in the near-infrared region of 900-1700 nm not only allows a deep tissue penetration depth but also offers the unique benefit of the quantitative visualization of molecular events in vivo and is independent of local luminescence intensity and fluorophore concentration. Herein, we report the design of a wide-range pH sensitive molecular probe based on Yb3+ porphyrinate. The Yb3+ probe shows increasing NIR emission and lifetime with pK a values of ca. 6.6 from pH 9.0 and 5.0 and also displays an elongated lifetime from ca. 135 to 170 µs at lower pH values (5.0-1.0) due to aggregation and reduced exposure to water at low pH values. Importantly, the probe is able to monitor a wide range of in vivo gastrointestinal pH values in mice models and the potential applications in imaging-guided gastrointestinal diagnostics and therapeutics were revealed. This study shows that lifetime contrast is important for preclinical imaging; lanthanide complexes could be successfully used in the design of stimuli-responsive NIR τ probes for advanced in vivo imaging.

17.
ACS Appl Mater Interfaces ; 11(17): 15298-15305, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30977992

RESUMO

The difficulty of near-infrared (NIR) ratiometric detection imaging lies in the lack of high-efficiency NIR probes and the overlapping interference between two emission peaks. To achieve more accurate detection in living organisms, dual NIR-emissive luminescent nanoprobes were designed under the same excitation at 808 nm. The Er3+ ion-doped nanoparticles were employed as a reference with their fluorescence emission at 1525 nm. Meanwhile, a cyanine dye molecule (Cy925) was combined on the surface of nanoparticles as the ClO- recognition site with its NIR emission at 925 nm. The ratiometric nanoprobe relied on the ratio of aforementioned two separated NIR peaks ( I925nm/ I1525nm), featuring deeper imaging penetration depth and low autofluorescence. This nanoprobe was verified to be sensitive and highly selective to ClO- through photoluminescence titration. The in vitro detection experiment developed reasonable work curves, guaranteeing that we can detect the change in concentration of ClO- in mice limbs with arthritis through in vivo imaging experiments.


Assuntos
Corantes Fluorescentes/química , Ácido Hipocloroso/análise , Nanopartículas/química , Animais , Articulação do Tornozelo/diagnóstico por imagem , Artrite/induzido quimicamente , Artrite/diagnóstico por imagem , Carbocianinas/química , Extremidades/diagnóstico por imagem , Feminino , Fluoretos/química , Ácido Hipocloroso/química , Camundongos , Camundongos Endogâmicos BALB C , Espectroscopia de Luz Próxima ao Infravermelho , Ítrio/química
18.
ACS Cent Sci ; 5(2): 299-307, 2019 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-30834318

RESUMO

Luminescence imaging, exhibiting noninvasive, sensitive, rapid, and versatile properties, plays an important role in biomedical applications. It is usually unsuitable for direct biodetection, because the detected luminescence intensity can be influenced by various factors such as the luminescent substance concentration, the depth of the luminescent substance in the organism, etc. Ratiometric imaging may eliminate the interference due to the luminescent substance concentration on the working signal. However, the conventional ratiometric imaging mode has a limited capacity for in vivo signal acquisition and fidelity due to the highly variable and wavelength-dependent scattering and absorption process in biotissue. In this work, we demonstrate a general imaging mode in which two signals with the same working wavelength are used to perform ratiometric sensing ignoring the depth of the luminescent substance in the organism. Dual-channel decoding is achieved by time-gated imaging technology, in which the signals from lanthanide ions and fluorescent dyes are distinguished by their different luminescent lifetimes. The ratiometric signal is proven to be nonsensitive to the detection depth and excitation power densities; thus, we could utilize the working curve measured in vitro to determine the amount of target substance (hypochlorous acid) in vivo.

19.
Adv Sci (Weinh) ; 6(5): 1801834, 2019 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-30886806

RESUMO

Recently, upconversion luminescence (UCL) has been widely applied in bioimaging due to its low autofluorescence and high contrast. However, a relatively high power density is still needed in conventional UCL bioimaging. In the present study, an ultralow power density light, as low as 0.06 mW cm-2, is applied as an excitation source for UCL bioimaging with PbS/CdS/ZnS quantum dots (UCL-QDs) as probes. The speculated UCL mechanism is a phonon-assisted single-photon process, and the relative quantum yield is up to 4.6%. As determined by continuous irradiation with a 980 nm laser, the UCL-QDs show excellent photostability. Furthermore, UCL-QDs-based probe is applied in tumor, blood vessel, and lymph node bioimaging excited with an eye-safe low-power light-emitting diode light in a nude mouse with few heat effects.

20.
Nanoscale ; 11(6): 2959-2965, 2019 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-30693936

RESUMO

Ratiometric fluorescent sensors, which can provide a built-in correction for environmental effects, have attracted significant attention for analytical sensing and optical imaging with the potential to provide a precise and quantitative analysis. Herein, we report a strategy based on dye-sensitized upconversion for the design of dual-excitation upconverion ratiometric probes possessing same emission peaks under a large separation in the excitation spectra (980 nm and 808 nm). Specifically, effective enhancement of upconversion luminescence could be attributed to Cy787 dyes present on the surface of nanoparticles, and it subsequently decreased upon the addition of ClO- under an 808 nm irradiation, whereas the signal under 980 nm excitation remained essentially constant, thus allowing for quantitative ratiometric monitoring of ClO-. The rationally designed dye-sensitized upconverion nanosystem exhibits excellent sensitivity for ClO- with a quantification limit of 3.6 nM in aqueous solutions. We have also demonstrated that the designed nanoprobe is a promising material for semi-quantitative detection of ClO- in an arthritis mouse model.


Assuntos
Corantes Fluorescentes/metabolismo , Ácido Hipocloroso/análise , Nanocompostos/química , Nanotecnologia/métodos , Imagem Óptica/métodos , Animais , Artrite Experimental/diagnóstico por imagem , Camundongos
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