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1.
J Nanobiotechnology ; 22(1): 43, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38287357

RESUMO

The central nervous system (CNS) maintains homeostasis with its surrounding environment by restricting the ingress of large hydrophilic molecules, immune cells, pathogens, and other external harmful substances to the brain. This function relies heavily on the blood-cerebrospinal fluid (B-CSF) and blood-brain barrier (BBB). Although considerable research has examined the structure and function of the BBB, the B-CSF barrier has received little attention. Therapies for disorders associated with the central nervous system have the potential to benefit from targeting the B-CSF barrier to enhance medication penetration into the brain. In this study, we synthesized a nanoprobe ANG-PEG-UCNP capable of crossing the B-CSF barrier with high targeting specificity using a hydrocephalus model for noninvasive magnetic resonance ventriculography to understand the mechanism by which the CSF barrier may be crossed and identify therapeutic targets of CNS diseases. This magnetic resonance nanoprobe ANG-PEG-UCNP holds promising potential as a safe and effective means for accurately defining the ventricular anatomy and correctly locating sites of CSF obstruction.


Assuntos
Barreira Hematoencefálica , Encéfalo , Encéfalo/diagnóstico por imagem , Sistema Nervoso Central , Transporte Biológico/fisiologia , Imageamento por Ressonância Magnética
2.
Angew Chem Int Ed Engl ; 63(29): e202405913, 2024 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-38683647

RESUMO

Inactivating hyperactivated transcription factors can overcome tumor therapy resistance, but their undruggable features limit the development of conventional inhibitors. Here, we report that carbon-centered free radicals (R⋅) can inactivate NF-κB transcription by capping the active sites in both NF-κB and DNA. We construct a type of thermosensitive R⋅ initiator loaded amphiphilic nano-micelles to facilitate intracellular delivery of R⋅. At a temperature of 43 °C, the generated R⋅ engage in electrophilic radical addition towards double bonds in nucleotide bases, and simultaneously cap the sulfhydryl residues in NF-κB through radical chain reaction. As a result, both NF-κB nuclear translocation and NF-κB-DNA binding are suppressed, leading to a remarkable NF-κB inhibition of up to 94.1 %. We have further applied R⋅ micelles in a clinical radiofrequency ablation tumor therapy model, showing remarkable NF-κB inactivation and consequently tumor metastasis inhibition. Radical capping strategy not only provides a method to solve the heat-sink effect in clinic tumor hyperthermia, but also suggests a new perspective for controllable modification of biomacromolecules in cancer therapy.


Assuntos
Carbono , NF-kappa B , NF-kappa B/metabolismo , NF-kappa B/antagonistas & inibidores , Radicais Livres/química , Radicais Livres/metabolismo , Humanos , Carbono/química , Micelas , DNA/química , DNA/metabolismo , Animais , Camundongos
3.
Analyst ; 145(20): 6579-6585, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32780031

RESUMO

Aberrant accumulation of Amyloid-ß (Aß) peptide is closely related to Alzheimer's disease. Thus, it is important to develop featured probes for the specific detection of Aß species. Herein, we designed and synthesized a novel near-infrared fluorescent probe SDPY based on the D-π-A architecture for the detection of Aß aggregates. The probe SDPY displayed higher affinity for Aß40 aggregates over Aß42 aggregates in solution (Kd = 164 nM vs. 2.1 µM). In addition, SDPY showed excellent anti-interference against a wide range of other substances. Furthermore, SDPY was capable of labeling Aß40 aggregates better than Aß42 aggregates in the brain sections of AD transgenic mouse models.


Assuntos
Doença de Alzheimer , Corantes Fluorescentes , Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/metabolismo , Camundongos , Camundongos Transgênicos , Fragmentos de Peptídeos
4.
Molecules ; 24(2)2019 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-30669489

RESUMO

In recent years, rare earth doped upconversion nanocrystals have been widely used in different fields owing to their unique merits. Although rare earth chlorides and trifluoroacetates are commonly used precursors for the synthesis of nanocrystals, they have certain disadvantages. For example, rare earth chlorides are expensive and rare earth trifluoroacetates produce toxic gases during the reaction. To overcome these drawbacks, we use the less expensive rare earth hydroxide as a precursor to synthesize ß-NaYF4 nanoparticles with multiform shapes and sizes. Small-sized nanocrystals (15 nm) can be obtained by precisely controlling the synthesis conditions. Compared with the previous methods, the current method is more facile and has lower cost. In addition, the defects of the nanocrystal surface are reduced through constructing core⁻shell structures, resulting in enhanced upconversion luminescence intensity.


Assuntos
Fluoretos/síntese química , Hidróxidos/química , Substâncias Luminescentes/química , Metais Terras Raras/química , Nanopartículas/química , Luminescência , Medições Luminescentes , Tamanho da Partícula , Propriedades de Superfície , Ítrio
5.
Nat Commun ; 15(1): 8036, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39271701

RESUMO

Molecular imaging holds the potential for noninvasive and accurate grading of liver fibrosis. It is limited by the lack of biomarkers that strongly correlate with liver fibrosis grade. Here, we discover the grading potential of fibroblast activation protein alpha (FAPα) for liver fibrosis through transcriptional analysis and biological assays on clinical liver samples. The protein and mRNA expression of FAPα are linearly correlated with fibrosis grade (R2 = 0.89 and 0.91, respectively). A FAPα-responsive MRI molecular nanoprobe is prepared for quantitatively grading liver fibrosis. The nanoprobe is composed of superparamagnetic amorphous iron nanoparticles (AFeNPs) and paramagnetic gadoteric acid (Gd-DOTA) connected by FAPα-responsive peptide chains (ASGPAGPA). As liver fibrosis worsens, the increased FAPα cut off more ASGPAGPA, restoring a higher T1-MRI signal of Gd-DOTA. Otherwise, the signal remains quenched due to the distance-dependent magnetic resonance tuning (MRET) effect between AFeNPs and Gd-DOTA. The nanoprobe identifies F1, F2, F3, and F4 fibrosis, with area under the curve of 99.8%, 66.7%, 70.4%, and 96.3% in patients' samples, respectively. This strategy exhibits potential in utilizing molecular imaging for the early detection and grading of liver fibrosis in the clinic.


Assuntos
Endopeptidases , Cirrose Hepática , Imageamento por Ressonância Magnética , Proteínas de Membrana , Cirrose Hepática/diagnóstico por imagem , Cirrose Hepática/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Endopeptidases/metabolismo , Proteínas de Membrana/metabolismo , Gelatinases/metabolismo , Compostos Organometálicos/química , Masculino , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/metabolismo , Feminino , Compostos Heterocíclicos/química , Pessoa de Meia-Idade , Animais , Meios de Contraste/química
6.
J Funct Biomater ; 14(4)2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37103297

RESUMO

The development of nanosystems, which can photooxygenate amyloid-ß (Aß), detect the Tau protein, and inhibit effectively the Tau aggregation, is increasingly important in the diagnosis and therapy of Alzheimer's disease (AD). Herein, UCNPs-LMB/VQIVYK (UCNPs: upconversion nanoparticles, LMB: Leucomethylene blue, and VQIVYK: Biocompatible peptide) is designed as a HOCl-controlled released nanosystem for AD synergistic treatment. Under exposure to high levels of HOCl, the released MB from UCNPs-LMB/VQIVYK will produce singlet oxygen (1O2) under red light to depolymerize Aß aggregation and reduce cytotoxicity. Meanwhile, UCNPs-LMB/VQIVYK can act as an inhibitor to decrease Tau-induced neurotoxicity. Besides, UCNPs-LMB/VQIVYK can be used for upconversion luminescence (UCL) due to its unexceptionable luminescence properties. This HOCl-responsive nanosystem offers a new therapy for AD treatment.

7.
Adv Sci (Weinh) ; 10(34): e2304668, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37870166

RESUMO

Positive computed tomography (CT) contrast nanoagent has significant applications in diagnosing tumors. However, the sensitive differentiation between hepatoma and normal liver tissue remains challenging. This challenge arises primarily because both normal liver and hepatoma tissues capture the nanoagent, resulting in similar positive CT contrasts. Here, a strategy for fusing positive and negative CT contrast nanoagent is proposed to detect hepatoma. A nanoagent Hf-MOF@AB@PVP initially generates a positive CT contrast signal of 120.3 HU in the liver. Subsequently, it can specifically respond to the acidic microenvironment of hepatoma to generate H2 , further achieving a negative contrast of -96.0 HU. More importantly, the relative position between the negative and positive signals area is helpful to determine the location of hepatoma and normal liver tissues. The distinct contrast difference of 216.3 HU and relative orientation between normal liver and tumor tissues are meaningful to sensitively distinguish hepatoma from normal liver tissue utilizing CT imaging.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Meios de Contraste , Microambiente Tumoral
8.
Adv Mater ; 35(18): e2211597, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36746119

RESUMO

The spatiotemporal characterization of signaling crosstalk between subcellular organelles is crucial for the therapeutic effect of malignant tumors. Blocking interactive crosstalk in this fashion is significant but challenging. Herein, a communication interception strategy is reported, which blocks spatiotemporal crosstalk between subcellular organelles for cancer therapy with underlying molecular mechanisms. Briefly, amorphous-core@crystalline-shell Fe@Fe3 O4 nanoparticles (ACFeNPs) are fabricated to specifically block the crosstalk between lysosomes and endoplasmic reticulum (ER) by hydroxyl radicals generated along with their trajectory through heterogeneous Fenton reaction. ACFeNPs initially enter lysosomes and trigger autophagy, then continuous lysosomal damage blocks the generation of functional autolysosomes, which mediates ER-lysosome crosstalk, thus the autophagy is paralyzed. Thereafter, released ACFeNPs from lysosomes induce ER stress. Without the alleviation by autophagy, the ER-stress-associated apoptotic pathway is fully activated, resulting in a remarkable therapeutic effect. This strategy provides a wide venue for nanomedicine to exert biological advantages and confers new perspective for the design of novel anticancer drugs.


Assuntos
Estresse do Retículo Endoplasmático , Neoplasias , Neoplasias/metabolismo , Autofagia , Lisossomos/metabolismo , Humanos
9.
Chem Sci ; 13(8): 2202-2217, 2022 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-35310479

RESUMO

Redox homeostasis, as an innate cellular defense mechanism, not only contributes to malignant transformation and metastasis of tumors, but also seriously restricts reactive oxygen species (ROS)-mediated tumor therapies, such as chemotherapy, radiotherapy, photodynamic therapy (PDT), and chemodynamic therapy (CDT). Therefore, the development of the redox dyshomeostasis (RDH) strategy based on nanomaterials chemistry is of great significance for developing highly efficient tumor therapy. This review will firstly introduce the basic definition and function of cellular redox homeostasis and RDH. Subsequently, the current representative progress of the nanomaterial-based RDH strategy for tumor therapy is evaluated, summarized and discussed. This strategy can be categorized into three groups: (1) regulation of oxidizing species; (2) regulation of reducing species and (3) regulation of both of them. Furthermore, the current limitations and potential future directions for this field will be briefly discussed. We expect that this review could attract positive attention in the chemistry, materials science, and biomedicine fields and further promote their interdisciplinary integration.

10.
Front Chem ; 10: 890545, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35615313

RESUMO

Singlet oxygen (1O2) is a common reactive oxygen species that has found wide application in wastewater processing, photochemical synthesis, and photodynamic therapy. In this paper, a dual-core metal [a Re(I)-based component and a Gd(III)-based component] photosensitizer was synthesized and doped into polymer fibrous films for 1O2 generation. Here the Re(I)-based component is responsible for the photosensitizing reaction which directly transformed 3O2 to 1O2, while the Gd(III)-based component served as an auxiliary part that assisted the transformation from 3O2 to 1O2 via synergistic effect by its triplet excited ligands. The photophysical parameters of this photosensitizer (denoted as Re-Gd) and its fibrous films (denoted as Re-Gd@PVP) were carefully recorded, discussed, and compared. It was found that the excited state lifetime and photostability of Re-Gd were both improved after being doped into fibrous films, favoring 1O2 generation. The 1O2 generation performance comparison between Re-Gd in the solid state, in solution, and fibrous films suggested that 1O2 generation performance was indeed improved by the electrospinning films. In addition, the positive factor of synergistic effect on improving 1O2-producing efficiency was confirmed by comparing Re-Gd@PVP films with reference films with a single-core metal photosensitizer having no synergistic effect.

11.
ACS Nano ; 16(3): 4217-4227, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35254050

RESUMO

B-mode ultrasound imaging is a significant anatomic technique in clinic, which can display the anatomic variation in tissues. However, it is difficult to evaluate the functional state of organs and display the physiological information in organisms such as the tumor acidic microenvironment (TME). Herein, inspired by the phenomenon of sonographic acoustic shadow during detecting calculus in clinic, a strategy of self-enhanced acoustic impedance difference is proposed to monitor the acidic TME. BiF3@PDA@PEG (BPP) nanoparticles can self-aggregate in a specific response to the acidic TME to form huge "stones" BiF3@PDA, resulting in an increase of local tumor density, and further causing a significant acoustic impedance difference. In in vitro experiments, the enhanced ultrasound signals change from 15.2 to 196.4 dB, which can discriminate different pH values from 7.0 to 5.0, and the sensitivity can reach to 0.2 value. In in vivo experiments, the enhanced ultrasound signal is 107.7 dB after BPP self-aggregated, displaying the weak acidic TME that has a close relationship with the size and species of the tumor. More importantly, the accuracy is away from the interference of pressure because huge "stones" BiF3@PDA change little. However, SonoVue microbubbles will diffuse and rupture under pressure, which results in false positive signals. To sum up, this strategy will be helpful to the further development of ultrasound molecular imaging.


Assuntos
Nanopartículas , Microambiente Tumoral , Acústica , Impedância Elétrica , Microbolhas , Nanopartículas/química
12.
J Org Chem ; 75(17): 6043-5, 2010 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-20795749

RESUMO

A palladium-catalyzed addition of arylboronic acids to phthalaldehyde, followed by an intramolecular lactonization to access 3-substituted phthalides, is described. The procedure tolerates a series of functional groups, such as methoxyl, fluoro, chloro, and trifluoromethyl groups. It represents a procedure for the synthesis of 3-substituted phthalides.


Assuntos
Benzofuranos/síntese química , Lactonas/química , Paládio/química , o-Ftalaldeído/química , Benzofuranos/química , Ácidos Borônicos/química , Catálise , Ciclização , Estrutura Molecular , Estereoisomerismo
13.
Mol Biol Rep ; 37(2): 875-92, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19672692

RESUMO

In order to understand the mechanism of the strong resistance of Oryza granulata to Xanthomonas oryzae pv oryzae (Xoo), cDNA microarrays containing 2,436 cDNA clones of Oryza granulata derived from Suppression subtractive library and cDNA library were constructed and genome expression patterns after inoculating Xoo were investigated. Three hundred and 83 clones were up-regulated, 836 clones were down-regulated after pathogen infection. Approximately 800 clones were sequenced and BLAST search were carried out. There are no homologous sequences for 35 clones of them. The functions of the homologous sequences for most clones are unknown. The known functions of the homologous sequences involved in photosynthesis, respiration, material transport, signal transduction, pathogenesis-related proteins, transcription factors, the active oxygen scavenging system and so on. The putative functions of them in responding to Xoo were discussed.


Assuntos
Regulação da Expressão Gênica de Plantas , Genoma de Planta , Oryza/genética , Doenças das Plantas/genética , Xanthomonas/patogenicidade , Sequência de Aminoácidos , Perfilação da Expressão Gênica , Biblioteca Genômica , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Dados de Sequência Molecular , Análise de Sequência com Séries de Oligonucleotídeos , Oryza/imunologia , Filogenia , Doenças das Plantas/imunologia , Proteínas de Plantas/genética , Homologia de Sequência de Aminoácidos , Xanthomonas/imunologia
15.
Chem Asian J ; 15(18): 2864-2867, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32720435

RESUMO

It is well known that copper ions play a critical role in various physiological processes. However, a variety of human diseases are tightly correlated with copper overload. Although there are numerous fluorescent probes capable of detecting copper ions, most of them are "turn-off" probes owing to copper (II) ions fluorescence quenching effect, resulting in poor sensitivity. Herein, a novel "turn-on" near-infrared (NIR) fluorescent probe PZ-N based on phenoxazine was designed and synthesized for the selective detection of copper (II) ions (Cu2+ ). Upon the addition of Cu2+ , the probe could quickly react with Cu2+ and emit strong fluorescence, along with colour change from colourless to obvious blue. Moreover, the probe PZ-N showed good water solubility, high selectivity, and excellent sensitivity with low limit of detection (1.93 nM) towards copper (II) ions. More importantly, PZ-N was capable of effectively detecting Cu2+ in living cells.


Assuntos
Cobre/análise , Corantes Fluorescentes/química , Oxazinas/química , Cobre/metabolismo , Células HeLa , Humanos , Íons/química , Azul de Metileno/química , Microscopia de Fluorescência , Espectrometria de Fluorescência
16.
J Mater Chem B ; 7(36): 5535-5540, 2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31451829

RESUMO

Two quinoline-malononitrile-based NIR fluorescent probes with good water-solubility have been developed for detecting and imaging of Aß aggregates in Alzheimer's disease. In vitro studies demonstrated that both probes exhibited high affinity to Aß aggregates with an increase of fluorescence intensity due to the intramolecular charge transfer effect. Moreover, the probes could particularly image Aß plaques in brain sections of triple transgenic AD mice.


Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/química , Corantes Fluorescentes/química , Água/química , Animais , Raios Infravermelhos , Camundongos , Camundongos Transgênicos , Estrutura Molecular , Tamanho da Partícula , Agregados Proteicos , Teoria Quântica , Solubilidade , Propriedades de Superfície
17.
Chem Commun (Camb) ; 52(57): 8865-8, 2016 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-27346489

RESUMO

We report a new spiropyran-based fluorescent probe that exhibits high affinity and specificity towards Aß oligomers both in vitro and in vivo. This probe can penetrate the blood brain barrier and specifically target Aß oligomers in the brains of transgenic mice in models for Alzheimer's disease.


Assuntos
Doença de Alzheimer/diagnóstico , Peptídeos beta-Amiloides/análise , Benzopiranos/química , Corantes Fluorescentes/química , Indóis/química , Nitrocompostos/química , Animais , Benzopiranos/administração & dosagem , Modelos Animais de Doenças , Fluorescência , Corantes Fluorescentes/administração & dosagem , Indóis/administração & dosagem , Injeções Intraperitoneais , Camundongos , Camundongos Transgênicos , Estrutura Molecular , Nitrocompostos/administração & dosagem , Teoria Quântica
19.
Chem Commun (Camb) ; 51(1): 125-8, 2015 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-25384304

RESUMO

Two fluorescent switchable diarylethene derivatives which exhibit high affinity for amyloid-ß aggregates with the increase of fluorescence intensity were reported. Moreover, the probes show excellent photochromic and anti-photobleaching properties both in vitro and in vivo.


Assuntos
Peptídeos beta-Amiloides/análise , Corantes Fluorescentes/química , Microscopia de Fluorescência , Doença de Alzheimer/patologia , Encéfalo/metabolismo , Encéfalo/patologia , Curcumina/química , Corantes Fluorescentes/síntese química , Humanos
20.
Chem Commun (Camb) ; 51(30): 6667-70, 2015 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-25784588

RESUMO

Photochromism in a diarylethene derivative (1O) can be gated by a host-guest interaction where the thiazole orange groups are bound into the hydrophobic cavity of CB[8] in water. The closed-ring isomer (1C), which cannot be obtained freely in aqueous solution, survives even when the complex is dissociated by displacement from CB[8] by competition with 1-adamantanamine hydrochloride.

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