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The practical application of organic fluorophores in bioimaging is severely limited due to their generally poor stability. In this Highlight, we emphasize several representative strategies including nanoparticle-encapsulating dyes, dye-doped nanoparticles and molecular engineering for stabilizing fluorophores, especially with a breakthrough in photostability for visualizing disease therapy, tumor and biological processes.
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Corantes Fluorescentes/química , Imagem Óptica/métodos , HumanosRESUMO
In vivo monitoring of the biodistribution and activation of prodrugs is urgently required. Near infrared (NIR) fluorescence-active fluorophores with excellent photostability are preferable for tracking drug release in vivo. Herein, we describe a NIR prodrug DCM-S-CPT and its polyethylene glycol-polylactic acid (PEG-PLA) loaded nanoparticles as a potent cancer therapy. We have conjugated a dicyanomethylene-4H-pyran derivative as the NIR fluorophore with camptothecin (CPT) as the anticancer drug using a disulfide linker. In vitro experiments verify that the high intracellular glutathione (GSH) concentrations in tumor cells cause cleavage of the disulfide linker, resulting in concomitantly the active drug CPT release and significant NIR fluorescence turn-on with large Stokes shift (200 nm). The NIR fluorescence of DCM-S-CPT at 665 nm with fast response to GSH can act as a direct off-on signal reporter for the GSH-activatable prodrug. Particularly, DCM-S-CPT possesses much better photostability than ICG, which is highly desirable for in situ fluorescence-tracking of cancer chemotherapy. DCM-S-CPT has been successfully utilized for in vivo and in situ tracking of drug release and cancer therapeutic efficacy in living animals by NIR fluorescence. DCM-S-CPT exhibits excellent tumor-activatable performance when intravenously injected into tumor-bearing nude mice, as well as specific cancer therapy with few side effects. DCM-S-CPT loaded in PEG-PLA nanoparticles shows even higher antitumor activity than free CPT, and is also retained longer in the plasma. The tumor-targeting ability and the specific drug release in tumors make DCM-S-CPT as a promising prodrug, providing significant advances toward deeper understanding and exploration of theranostic drug-delivery systems.
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Corantes Fluorescentes/uso terapêutico , Raios Infravermelhos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Pró-Fármacos/uso terapêutico , Animais , Linhagem Celular Tumoral , Estabilidade de Medicamentos , Corantes Fluorescentes/química , Corantes Fluorescentes/metabolismo , Glutationa/metabolismo , Humanos , Espaço Intracelular/metabolismo , Ácido Láctico/química , Camundongos , Imagem Molecular , Nanopartículas/química , Poliésteres , Polietilenoglicóis/química , Polímeros/química , Pró-Fármacos/química , Pró-Fármacos/metabolismoRESUMO
Cancer cells typically display redox imbalance compared with normal cells due to increased metabolic rate, accumulated mitochondrial dysfunction, elevated cell signaling, and accelerated peroxisomal activities. This redox imbalance may regulate gene expression, alter protein stability, and modulate existing cellular programs, resulting in inefficient treatment modalities. Therapeutic strategies targeting intra- or extracellular redox states of cancer cells at varying state of progression may trigger programmed cell death if exceeded a certain threshold, enabling therapeutic selectivity and overcoming cancer resistance to radiotherapy and chemotherapy. Nanotechnology provides new opportunities for modulating redox state in cancer cells due to their excellent designability and high reactivity. Various nanomaterials are widely researched to enhance highly reactive substances (free radicals) production, disrupt the endogenous antioxidant defense systems, or both. Here, the physiological features of redox imbalance in cancer cells are described and the challenges in modulating redox state in cancer cells are illustrated. Then, nanomaterials that regulate redox imbalance are classified and elaborated upon based on their ability to target redox regulations. Finally, the future perspectives in this field are proposed. It is hoped this review provides guidance for the design of nanomaterials-based approaches involving modulating intra- or extracellular redox states for cancer therapy, especially for cancers resistant to radiotherapy or chemotherapy, etc.
Assuntos
Nanoestruturas , Neoplasias , Oxirredução , Humanos , Neoplasias/metabolismo , Neoplasias/terapia , Nanoestruturas/uso terapêutico , AnimaisRESUMO
Three tricarbocyanine dyes (IR-897, IR-877, and IR-925) with different thiourea substituents that function as dosimeter units through specific Hg(2+)-induced desulfurization have been demonstrated in a fast indicator paper for Hg(2+) and MeHg(+) ions. In comparison with available Hg(2+)-selective chemodosimeters, IR-897 and IR-877 show several advantages, such as convenient synthesis, very long wavelengths falling in the near-infrared (NIR) region (650-900â nm) with high molar extinction coefficients, a ratiometric response, and quite low disturbance with Ag(+) and Cu(2+) ions. They exhibit large redshifts, which result in a clear color change from deep blue to pea green that can be easily monitored by the naked eye for a convenient indicator paper. In emission spectra, they display a characteristic turn-off mode at 780â nm and turn-on mode at 830â nm with titration of Hg(2+) ions. Remarkably, the signal/noise (S/N) ratio with other thiophilic metal ions (Ag(+) and Cu(2+)) is greatly enhanced with ratiometric measurement of two channels: excitation spectra mode (I(810â nm)/I(670â nm), monitored at 830â nm) and emission spectra mode (I(830â nm)/I(780â nm), isosbestic absorption point at 730â nm as excitation). The distinct response is dependent upon the electron-donating effect of the thiourea substituents; that is, the stronger the electron-donating capability of the thiourea substituents, the faster the Hg(2+)-promoted cyclization. Additionally, experiments with living SW1116 cells show that these three tricarbocyanine dyes with low toxicity can exhibit special characteristics that are favorable for visualizing intracellular Hg(2+) and MeHg(+) ions in biological systems, including excellent membrane permeability, minimal interfering absorption and fluorescence from biological samples, low scattering, and deep penetration into tissues.
Assuntos
Carbocianinas/síntese química , Corantes/síntese química , Corantes Fluorescentes/síntese química , Mercúrio/análise , Carbocianinas/química , Corantes/química , Corantes Fluorescentes/química , Estrutura Molecular , Espectroscopia de Luz Próxima ao InfravermelhoRESUMO
Uranium, a double-edged sword with high-efficiency energy and radioactive toxicity, attracts people to enjoy the advantages by generating power, but at the same time brings potential harm by nuclide migration. Therefore, it is necessary to develop a highly-efficient sensor to monitor uranyl ions in the field. However, the designed processes of the reported sensors are random, time-consuming and difficulty. It is urgent to find a new strategy to rationally, quickly and effectively screen out the required molecule for efficient uranium detection. Herein, with the guidance from the rational design method, the parameter, Egap, was applied to judge the chromatic aberration between the designed PADAP derivate and its uranyl complex. And the optimized structure sensor, 2-((3-bromo-5-(9,9-dioctyl-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-9H-fluoren-2-yl)-2-pyridylazo)-5-(diethylamino)phenol (abbr. W1H), was screened and successfully synthesized. W1H exhibited significant color change (red to blue) after binding uranyl ions, and its detection limit for uranium was as low as nanomolar. More meaningfully, the coordination mechanism of W1H toward uranium was clarified by theoretical calculation of the electron cloud density distribution, Ebind, and 1H NMR, IR and MS for the first time. With the more excellent uranyl sensitivity, selectivity, and recyclability, W1H and its colorimetric test strip have been applied to the detection of low-concentration uranium in environmental samples around the uranium tailings, providing a useful on-site method to monitor trace uranium in actual samples.
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The magnetic poly(N-isopropylacrylamide)/chitosan hydrogel with interpenetrating network (IPN) structure was designed based on the functional groups of targeted emerging contaminants, represented by hydrophilic sulfamethoxazole (SMZ) and hydrophobic bisphenol A (BPA). The average particle size, specific surface area, and total pore volume of the hydrogel were turned out to be 103.7⯵m, 60.70â¯m2/g and 0.0672â¯cm3/g, respectively. Adsorption results indicated that the maximum adsorption capacity occurred at the pH where SMZ was anionic and BPA was uncharged. When the adsorption temperature increased from 25⯰C to 35⯰C, the amount of adsorbed SMZ hardly changed, but that of BPA increased by two times. The adsorption capacity of the binary system (i.e., with both SMZ and BPA) was almost the same as that of the single system, indicating that simultaneous adsorption of SMZ and BPA was achieved. The adsorption equilibrium was reached quickly (within 5â¯min) for both SMZ and BPA. For adsorption isotherm, the Freundlich model fitted well for SMZ at 25, 35 and 45⯰C. However, the adsorption of BPA exhibited the sigmoidally shaped isotherm at 25⯰C with the Slips model fitting well, and both the Freundlich isotherm and the Slips isotherm fitted the data well at 35⯰C and 45⯰C, suggesting that the adsorption force was initially weak but greatly enhanced with an increase in adsorbate concentration or ambient temperature. The main adsorption mechanism was inferred to be electrostatic interactions for SMZ, and hydrophobic interactions as well as hydrogen bonding for BPA. The hydrogel adsorbent maintained favorable adsorption capacity for BPA after five adsorption-desorption cycles. These findings may provide a strategy for designing high performance adsorbents that can remove both hydrophilic and hydrophobic organic contaminants in the aquatic environment.
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Targeted bioimaging or chemotherapeutic drug delivery to achieve the desired therapeutic effects while minimizing side effects has attracted considerable research attention and remains a clinical challenge. Presented herein is a multi-component delivery system based on carbohydrate-functionalized gold nanoparticles conjugated with a fluorophore or prodrug. The system leverages active targeting based on carbohydrate-lectin interactions and release of the payload by biological thiols. Cell-type specific delivery of the activatable fluorophore was examined by confocal imaging on HepG2 cells, and displays distinct selectivity towards HepG2 cells over HeLa and NIH3T3 cells. The system was further developed into a drug delivery vehicle with camptothecin (CPT) as a model drug. It was demonstrated that the complex exhibits similar cytotoxicity to that of free CPT towards HepG2 cells, and is significantly less cytotoxic to normal HDF and NIH3T3 cells, indicating excellent specificity. The delivery vehicle itself exhibits excellent biocompatibility and offers an attractive strategy for cell-type specific delivery depending on the carbohydrates conjugated in the system.
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A novel near-infrared (NIR) and colorimetric fluorescent molecular probe based on a dicyanomethylene-4H-pyran chromophore for the selective detection of glutathione in living cells has been developed. The fluorescence OFF-ON switch is triggered by cleavage of the 2,4-dinitrobenzensulfonyl (DNBS) unit by the interaction with GSH.
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Técnicas de Química Analítica/instrumentação , Glutationa/análise , Raios Infravermelhos , Sobrevivência Celular , Colorimetria , Glutationa/química , Células HeLa , Humanos , Espectrometria de FluorescênciaRESUMO
The donor-acceptor system of indoline-benzothiadiazole is established as the novel and reactive platform for generating amine radical cations with the interaction of Cu(2+), which has been successfully exploited as the building block to be highly sensitive and selective near infrared (NIR) colorimetric and fluorescent Cu(2+) sensors. Upon the addition of Cu(2+), an instantaneous red shift of absorption spectra as well as the quenched NIR fluorescence of the substrates is observed. The feasibility and validity of the radical cation generation are confirmed by cyclic voltammetry and electron paramagnetic resonance spectra. Moreover, the introduction of an aldehyde group extends the electron spin density and changes the charge distribution. Our system demonstrates the large scope and diversity in terms of activation mechanism, response time, and property control in the design of Cu(2+) sensors.
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Hydrophilic, fluorescent hybrid nanoprobes (NDI@HNPs) encapsulated with the hydrophobic pH-responsive fluorophore (N,N'-di-n-dodecyl-2,6-di(4-methyl-piperazin-1-yl)naphthalene-1,4,5,8-tetracarboxylic acid diimide, NDI) for recognizing and mapping the route of cell phagocytosis have been fabricated based on the self-assembly of amphiphilic diblock copolymer PS-b-PAA and the subsequent shell cross-linking with 3-mercaptopropyltrimethoxy silane (MPTMS). The as-synthesized NDI@HNPs has a typical spherical morphology of 46 nm in diameter with excellent monodispersity in aqueous solution. The NDI@HNPs probe exhibits extremely low cytotoxicity, fast real time pH response and enhanced fluorescence intensity under acidic environment with respect to the corresponding free dye in highly polar aqueous system because of the encapsulation of NDI molecules inside nanoparticle cores with weak polarity environment. The fluorescence intensity of NDI@HNPs is enhanced by 55-fold upon changing from neutral (pH = 7.4) or basic (pH = 8.4) to acid (pH = 3.4) in aqueous system, in contrast to the serious fluorescence quenching of free NDI in the same medium, which can exactly meet the physiological pH range in cells. The favorably long emission wavelength is beneficial to the low scattering and minimal interfering requirements to fluorescent bioimaging. Moreover, functionalization with rapid cell-penetrating peptides (HIV-1 TAT) allows them to overcome the physiological and biological barriers during the phagocytosis process. Its characteristic fluorescent response to pH benefits the intracellular labeling and organelle targeting, realizing the real time tracking of the probe entry into cancer cells, the accumulation into the endolysosome and the further escape.
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Técnicas Biossensoriais , Nanopartículas/química , Polímeros/química , Linhagem Celular Tumoral , Endocitose/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Estrutura MolecularRESUMO
A novel fluorescent sensor DCAA-Cu(2+) was developed, showing turn-on fluorescence in NIR region with high selectivity to pyrophosphate anion in 100% aqueous solution.
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Benzopiranos/química , Cobre/química , Difosfatos/análise , Corantes Fluorescentes/química , Espectrometria de Fluorescência/métodos , Ânions/análise , Linhagem Celular Tumoral , Humanos , Sensibilidade e Especificidade , Água/químicaRESUMO
Water-soluble hydrophobic-dye@nano-hybrids (DPN@NHs) with extraordinarily enhanced fluorescent performance were fabricated by encapsulating the hydrophobic dye molecules into the core of the hybrid nanospheres based on the self-assembly of amphiphilic block copolymers followed by shell cross-linking using 3-mercaptopropyltrimethoxy-silane. The DPN@NHs are 50 nm in size, are monodispersed in aqueous solution and have a quantum yield enhanced by 30 times.