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1.
Adv Sci (Weinh) ; 11(22): e2310211, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38460166

RESUMO

The precise targeted delivery of therapeutic agents to deep regions of the brain is crucial for the effective treatment of various neurological diseases. However, achieving this goal is challenging due to the presence of the blood‒brain barrier (BBB) and the complex anatomy of the brain. Here, a biomimetic self-propelled nanomotor with cascade targeting capacity is developed for the treatment of neurological inflammatory diseases. The self-propelled nanomotors are designed with biomimetic asymmetric structures with a mesoporous SiO2 head and multiple MnO2 tentacles. Macrophage membrane biomimetic modification endows nanomotors with inflammatory targeting and BBB penetration abilities The MnO2 agents catalyze the degradation of H2O2 into O2, not only by reducing brain inflammation but also by providing the driving force for deep brain penetration. Additionally, the mesoporous SiO2 head is loaded with curcumin, which actively regulates macrophage polarization from the M1 to the M2 phenotype. All in vitro cell, organoid model, and in vivo animal experiments confirmed the effectiveness of the biomimetic self-propelled nanomotors in precise targeting, deep brain penetration, anti-inflammatory, and nervous system function maintenance. Therefore, this study introduces a platform of biomimetic self-propelled nanomotors with inflammation targeting ability and active deep penetration for the treatment of neurological inflammation diseases.


Assuntos
Biomimética , Barreira Hematoencefálica , Dióxido de Silício , Animais , Dióxido de Silício/química , Camundongos , Biomimética/métodos , Barreira Hematoencefálica/metabolismo , Compostos de Manganês/química , Materiais Biomiméticos/química , Sistemas de Liberação de Medicamentos/métodos , Óxidos/química , Curcumina/uso terapêutico , Curcumina/farmacologia , Modelos Animais de Doenças , Doenças Neuroinflamatórias , Inflamação , Macrófagos , Encéfalo/metabolismo , Nanopartículas/química
2.
Nat Commun ; 14(1): 5140, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612298

RESUMO

The exogenous excitation requirement and electron-hole recombination are the key elements limiting the application of catalytic therapies. Here a tumor microenvironment (TME)-specific self-triggered thermoelectric nanoheterojunction (Bi0.5Sb1.5Te3/CaO2 nanosheets, BST/CaO2 NSs) with self-built-in electric field facilitated charge separation is fabricated. Upon exposure to TME, the CaO2 coating undergoes rapid hydrolysis, releasing Ca2+, H2O2, and heat. The resulting temperature difference on the BST NSs initiates a thermoelectric effect, driving reactive oxygen species production. H2O2 not only serves as a substrate supplement for ROS generation but also dysregulates Ca2+ channels, preventing Ca2+ efflux. This further exacerbates calcium overload-mediated therapy. Additionally, Ca2+ promotes DC maturation and tumor antigen presentation, facilitating immunotherapy. It is worth noting that the CaO2 NP coating hydrolyzes very slowly in normal cells, releasing Ca2+ and O2 without causing any adverse effects. Tumor-specific self-triggered thermoelectric nanoheterojunction combined catalytic therapy, ion interference therapy, and immunotherapy exhibit excellent antitumor performance in female mice.


Assuntos
Peróxido de Hidrogênio , Neoplasias , Feminino , Animais , Camundongos , Imunoterapia , Neoplasias/terapia , Apresentação de Antígeno , Transporte Biológico , Microambiente Tumoral
3.
Biochem Biophys Res Commun ; 526(3): 721-727, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32253032

RESUMO

The nucleocapsid protein (NC) of human immunodeficiency virus type 1 (HIV-1) is a small, highly basic nucleic acid (NA)-binding protein with two CCHC zinc-finger motifs. In this study, we report for the first time, to our knowledge, that thermal stressed HIV-1 NCp7 maintained NA-binding activity. About 41.3% of NCp7 remained soluble after incubated at 100 °C for 60 min, and heat-treated NCp7 maintained its abilities to bind to HIV-1 packaging signal (Psi) and the stem-loop 3 of the Psi. At high or very high degrees of sequence occupancy, NCp7 inhibited first-strand cDNA synthesis catalyzed by purified HIV-1 reverse transcriptase, and heat-treated NCp7 maintained the inhibition. Moreover, both EDTA-treated and H23K + H44K double mutant of NCp7 inhibited first-strand cDNA synthesis, demonstrating that the NA-binding activity of NCp7 at high NC:NA ratios is independent on its zinc-fingers. These results may benefit further investigations of the structural stability and function of NCp7 in viral replication.


Assuntos
HIV-1/química , RNA Viral/química , Produtos do Gene gag do Vírus da Imunodeficiência Humana/química , Sequência de Aminoácidos , Sítios de Ligação , DNA Complementar/biossíntese , Escherichia coli , Transcriptase Reversa do HIV/metabolismo , Resposta ao Choque Térmico , Humanos , Mutação , Ligação Proteica , Replicação Viral , Dedos de Zinco
4.
Environ Sci Pollut Res Int ; 27(30): 37313-37323, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31970635

RESUMO

The preparation, characterization, and uranium (VI) adsorption properties of tri-amidoxime modified marine fungus material (ZZF51-GPTS-EDA-AM/ZGEA) were investigated in this study. ZGEA was synthesized by four steps of condensation, nucleophilic substitution, electrophilic addition, and nitrile amidoxime and characterized by a series of methods containing FT-IR, TGA, SEM, and BET. Contrasted with uranium (VI) adsorption capacity of original fungus mycelium (15.46 mg g-1) that of the functional material (584.60 mg g-1) was great under the optimal factors such as uranium (VI) ion concentration 40 mg L-1, solid-liquid ratio 50 mg L-1, pH of solution 5.5, and reaction time 120 min. The above data were obtained by the orthogonal method. The cyclic tests showed that ZGEA had good regeneration performance, and it could be recycled at least five adsorption-desorption processes. The thermodynamic experimental adsorption result fitted Langmuir and Freundlich models, which explored monolayer and double layers of uranium (VI) adsorption mechanism, and the kinetic adsorption results were in better consistent with the pseudo-second-order and pseudo-first-order dynamic models (R2 > 0.999).


Assuntos
Urânio/análise , Adsorção , Fungos , Concentração de Íons de Hidrogênio , Cinética , Oximas , Espectroscopia de Infravermelho com Transformada de Fourier , Termodinâmica
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