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1.
Cells ; 11(2)2022 01 13.
Artigo em Inglês | MEDLINE | ID: mdl-35053389

RESUMO

Irreparable DNA damage following ionizing radiation (IR) triggers prolonged DNA damage response and induces premature senescence. Cellular senescence is a permanent state of cell-cycle arrest characterized by chromatin restructuring, altered nuclear morphology and acquisition of secretory phenotype, which contributes to senescence-related inflammation. However, the mechanistic connections for radiation-induced DNA damage that trigger these senescence-associated hallmarks are poorly understood. In our in vitro model of radiation-induced senescence, mass spectrometry-based proteomics was combined with high-resolution imaging techniques to investigate the interrelations between altered chromatin compaction, nuclear envelope destabilization and nucleo-cytoplasmic chromatin blebbing. Our findings confirm the general pathophysiology of the senescence-response, with disruption of nuclear lamin organization leading to extensive chromatin restructuring and destabilization of the nuclear membrane with release of chromatin fragments into the cytosol, thereby activating cGAS-STING-dependent interferon signaling. By serial block-face scanning electron microscopy (SBF-SEM) whole-cell datasets were acquired to investigate the morphological organization of senescent fibroblasts. High-resolution 3-dimensional (3D) reconstruction of the complex nuclear shape allows us to precisely visualize the segregation of nuclear blebs from the main nucleus and their fusion with lysosomes. By multi-view 3D electron microscopy, we identified nanotubular channels formed in lamin-perturbed nuclei of senescent fibroblasts; the potential role of these nucleo-cytoplasmic nanotubes for expulsion of damaged chromatin has to be examined.


Assuntos
Núcleo Celular/efeitos da radiação , Núcleo Celular/ultraestrutura , Senescência Celular/efeitos da radiação , Fibroblastos/efeitos da radiação , Fibroblastos/ultraestrutura , Imageamento Tridimensional , Microscopia Eletrônica , Radiação Ionizante , Linhagem Celular , Núcleo Celular/patologia , Forma Celular/efeitos da radiação , Montagem e Desmontagem da Cromatina , Fibroblastos/patologia , Humanos , Nanotubos/ultraestrutura , Proteômica
2.
Proc Natl Acad Sci U S A ; 119(4)2022 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-35042822

RESUMO

Functional and versatile nano- and microassemblies formed by biological molecules are found at all levels of life, from cell organelles to full organisms. Understanding the chemical and physicochemical determinants guiding the formation of these assemblies is crucial not only to understand the biological processes they carry out but also to mimic nature. Among the synthetic peptides forming well-defined nanostructures, the octapeptide Lanreotide has been considered one of the best characterized, in terms of both the atomic structure and its self-assembly process. In the present work, we determined the atomic structure of Lanreotide nanotubes at 2.5-Å resolution by cryoelectron microscopy (cryo-EM). Surprisingly, the asymmetric unit in the nanotube contains eight copies of the peptide, forming two tetramers. There are thus eight different environments for the peptide, and eight different conformations in the nanotube. The structure built from the cryo-EM map is strikingly different from the molecular model, largely based on X-ray fiber diffraction, proposed 20 y ago. Comparison of the nanotube with a crystal structure at 0.83-Å resolution of a Lanreotide derivative highlights the polymorphism for this peptide family. This work shows once again that higher-order assemblies formed by even well-characterized small peptides are very difficult to predict.


Assuntos
Nanotubos/química , Nanotubos/ultraestrutura , Peptídeos Cíclicos/química , Somatostatina/análogos & derivados , Microscopia Crioeletrônica/métodos , Modelos Moleculares , Peptídeos/química , Peptídeos Cíclicos/metabolismo , Somatostatina/química , Somatostatina/metabolismo , Difração de Raios X/métodos
3.
J Mater Sci Mater Med ; 33(1): 10, 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022850

RESUMO

Herein we report synthesis of hematite (α-Fe2O3) nanorods by calcinating hydrothermally synthesized goethite nanorods at 5000C. The structural, optical and MRI imaging guided cancer therapeutic properties of fabricated nanorods have been discussed in this manscript. FESEM and TEM imaging techniques were used to confirm the nanorod like morphology of as prepared materials. As we know that Fe2O3 nanorods with size in the range of 25-30 nm exhibit super magnetism. After coating with the PEG, the as prepared nanorods can be used as T2 MR imaging contrast agents. An excellent T2 MRI contrast of 38.763 mM-1s-1 achieved which is highest reported so far for α-Fe2O3. Besides the as prepared nanorods display an excellent photothermal conversion efficiency of 39.5% thus acts as an excellent photothermal therapeutic agent. Thus, we envision the idea of testing our nanorods for photothermal therapy and MR imaging application both in vitro and in vivo, achieving an excellent T2 MRI contrast and photothermal therapy effect with as prepared PEGylated nanorods.


Assuntos
Compostos Férricos/química , Nanotubos/química , Animais , Materiais Biocompatíveis/química , Linhagem Celular , Sobrevivência Celular , Feminino , Compostos Férricos/toxicidade , Células HeLa , Humanos , Técnicas In Vitro , Imageamento por Ressonância Magnética , Teste de Materiais , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Nus , Microscopia Eletrônica de Varredura , Nanotubos/toxicidade , Nanotubos/ultraestrutura , Neoplasias Experimentais/patologia , Neoplasias Experimentais/terapia , Fototerapia/métodos , Polietilenoglicóis/química , Análise Espectral Raman , Difração de Raios X
4.
Nat Nanotechnol ; 17(1): 98-106, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34795441

RESUMO

Cancer progresses by evading the immune system. Elucidating diverse immune evasion strategies is a critical step in the search for next-generation immunotherapies for cancer. Here we report that cancer cells can hijack the mitochondria from immune cells via physical nanotubes. Mitochondria are essential for metabolism and activation of immune cells. By using field-emission scanning electron microscopy, fluorophore-tagged mitochondrial transfer tracing and metabolic quantification, we demonstrate that the nanotube-mediated transfer of mitochondria from immune cells to cancer cells metabolically empowers the cancer cells and depletes the immune cells. Inhibiting the nanotube assembly machinery significantly reduced mitochondrial transfer and prevented the depletion of immune cells. Combining a farnesyltransferase and geranylgeranyltransferase 1 inhibitor, namely, L-778123, which partially inhibited nanotube formation and mitochondrial transfer, with a programmed cell death protein 1 immune checkpoint inhibitor improved the antitumour outcomes in an aggressive immunocompetent breast cancer model. Nanotube-mediated mitochondrial hijacking can emerge as a novel target for developing next-generation immunotherapy agents for cancer.


Assuntos
Leucócitos/patologia , Mitocôndrias/metabolismo , Nanotubos/química , Neoplasias/patologia , Animais , Sequência de Bases , Linhagem Celular Tumoral , Humanos , Imunidade , Camundongos Endogâmicos C57BL , Proteínas Mitocondriais/metabolismo , Nanotubos/ultraestrutura
5.
Biochem J ; 478(22): 3977-3998, 2021 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-34813650

RESUMO

Tunneling nanotubes (TNTs) are F-actin-based, membrane-enclosed tubular connections between animal cells that transport a variety of cellular cargo. Over the last 15 years since their discovery, TNTs have come to be recognized as key players in normal cell communication and organism development, and are also exploited for the spread of various microbial pathogens and major diseases like cancer and neurodegenerative disorders. TNTs have also been proposed as modalities for disseminating therapeutic drugs between cells. Despite the rapidly expanding and wide-ranging relevance of these structures in both health and disease, there is a glaring dearth of molecular mechanistic knowledge regarding the formation and function of these important but enigmatic structures. A series of fundamental steps are essential for the formation of functional nanotubes. The spatiotemporally controlled and directed modulation of cortical actin dynamics would be required to ensure outward F-actin polymerization. Local plasma membrane deformation to impart negative curvature and membrane addition at a rate commensurate with F-actin polymerization would enable outward TNT elongation. Extrinsic tactic cues, along with cognate intrinsic signaling, would be required to guide and stabilize the elongating TNT towards its intended target, followed by membrane fusion to create a functional TNT. Selected cargoes must be transported between connected cells through the action of molecular motors, before the TNT is retracted or destroyed. This review summarizes the current understanding of the molecular mechanisms regulating these steps, also highlighting areas that deserve future attention.


Assuntos
Comunicação Celular , Animais , Transporte Biológico , Linhagem Celular , Membrana Celular , Estruturas da Membrana Celular/imunologia , Estruturas da Membrana Celular/metabolismo , Estruturas da Membrana Celular/ultraestrutura , Humanos , Fusão de Membrana , Nanotubos/ultraestrutura
6.
Int J Biol Macromol ; 192: 869-882, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34634330

RESUMO

Injectable hydrogels have been known as promising materials for the regeneration of irregular shape tissue defects. In this study, novel thermosensitive methylcellulose (MC) hydrogels containing bassorin (Ba) and halloysite nanotubes (HNTs) have been developed for application in bone tissue engineering. Bassorin isolated from gum tragacanth (GT) with the concentration of 0.25-1.5 w/v% was blended with MC. The best MC/Ba gel (containing 0.5% bassorin) was chosen based on the results of injectability and rheological tests. HNTs (1-7%) were added to this formulation and tested for the physicochemical, mechanical, rheological, degradation, swelling, and biological properties. In vitro biological evaluations including cell proliferation (by MTT assay), cell attachment (by SEM), osteogenic activity (by Alizarin Red staining and alkaline phosphatase assay), and osteogenic gene expression (by quantitative real-time polymerase chain reaction) were done using MG-63 cells. Results showed that bassorin led to the increased gel-forming ability (at a lower temperature) and mechanical properties of MC hydrogel. The presence of HNTs and bassorin affected the degradation rate and swelling degree of MC-based hydrogel. Results showed significant enhancement in cell proliferation, differentiation, and mineralization, as well as higher bone-specific gene expression of the cell on bassorin and HNTs incorporated MC compared to pure MC hydrogel.


Assuntos
Regeneração Óssea , Fenômenos Químicos , Hidrogéis/química , Metilcelulose/química , Nanotubos/química , Tragacanto/química , Diferenciação Celular , Sobrevivência Celular , Fenômenos Mecânicos , Nanotubos/ultraestrutura , Porosidade , Reologia , Solubilidade , Análise Espectral , Engenharia Tecidual , Tecidos Suporte
7.
Lab Invest ; 101(12): 1571-1584, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34537825

RESUMO

Osteoclasts are multinucleated cells formed through specific recognition and fusion of mononuclear osteoclast precursors derived from hematopoietic stem cells. Detailed cellular events concerning cell fusion in osteoclast differentiation remain ambiguous. Tunneling nanotubes (TNTs), actin-based membrane structures, play an important role in intercellular communication between cells. We have previously reported the presence of TNTs in the fusion process of osteoclastogenesis. Here we analyzed morphological details of TNTs using scanning electron microscopy. The osteoclast precursor cell line RAW-D was stimulated to form osteoclast-like cells, and morphological details in the appearance of TNTs were extensively analyzed. Osteoclast-like cells could be classified into three types; early osteoclast precursors, late osteoclast precursors, and multinucleated osteoclast-like cells based on the morphological characteristics. TNTs were frequently observed among these three types of cells. TNTs could be classified into thin, medium, and thick TNTs based on the diameter and length. The shapes of TNTs were dynamically changed from thin to thick. Among them, medium TNTs were often observed between two remote cells, in which side branches attached to the culture substrates and beaded bulge-like structures were often observed. Cell-cell interaction through TNTs contributed to cell migration and rapid transport of information between cells. TNTs were shown to be involved in cell-cell fusion between osteoclast precursors and multinucleated osteoclast-like cells, in which movement of membrane vesicles and nuclei was observed. Formation of TNTs was also confirmed in primary cultures of osteoclasts. Furthermore, we have successfully detected TNTs formed between osteoclasts observed in the bone destruction sites of arthritic rats. Thus, formation of TNTs may be important for the differentiation of osteoclasts both in vitro and in vivo. TNTs could be one target cellular structure for the regulation of osteoclast differentiation and function in bone diseases.


Assuntos
Estruturas da Membrana Celular/ultraestrutura , Nanotubos/ultraestrutura , Osteogênese , Animais , Fusão Celular , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos Endogâmicos Lew
8.
Biol Futur ; 72(1): 25-36, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34554502

RESUMO

Nanotubular connections between mammalian cell types came into the focus only two decades ago, when "live cell super-resolution imaging" was introduced. Observations of these long-time overlooked structures led to understanding mechanisms of their growth/withdrawal and exploring some key genetic and signaling factors behind their formation. Unbelievable level of multiple supportive collaboration between tumor cells undergoing cytotoxic chemotherapy, cross-feeding" between independent bacterial strains or "cross-dressing" collaboration of immune cells promoting cellular immune response, all via nanotubes, have been explored recently. Key factors and "calling signals" determining the spatial directionality of their growth and their overall in vivo significance, however, still remained debated. Interestingly, prokaryotes, including even ancient archaebacteria, also seem to use such NT connections for intercellular communication. Herein, we will give a brief overview of current knowledge of membrane nanotubes and depict a simple model about their possible "historical role".


Assuntos
Comunicação Celular/fisiologia , Estruturas da Membrana Celular/fisiologia , Sistema Imunitário/fisiologia , Nanotubos/química , Animais , Transporte Biológico/fisiologia , Células Cultivadas , Humanos , Sistema Imunitário/citologia , Modelos Biológicos , Nanotubos/ultraestrutura , Células Procarióticas/fisiologia
9.
Int J Biol Macromol ; 189: 668-677, 2021 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-34453980

RESUMO

A general and effective strategy was developed for improving simultaneously the mechanical strength and antibacterial performance of biopolymer-based films. The well-dispersed zinc oxide (ZnO) nanoparticles were in-situ loaded on non-toxic natural palygorskite (PAL) nanorod to form an antibacterial PAL@ZnO composite nanorod, which can be embedded into chitosan/gelatin (CS/GL) film to produce the composite films with noticeably enhanced mechanical properties and antibacterial activity against S. aureus and E. coli bacteria (inhibition zones are 21.82 ± 0.95 mm and 16.36 ± 1.64 mm, respectively). The toughness of films enhances to 35.13 ± 0.95 MPa and the moisture uptake decreases to 23.74 ± 0.02% after embedding 3% and 9% of PAL@ZnO, respectively. In addition, incorporating PAL@ZnO nanorods also significantly enhanced the water resistance, and thermal stability of film. This work provides an alternative way for the development of antibacterial films with potential applications in many fields such as food packing.


Assuntos
Antibacterianos/farmacologia , Quitosana/química , Compostos de Magnésio/química , Nanotubos/química , Compostos de Silício/química , Óxido de Zinco/química , Adsorção , Escherichia coli/efeitos dos fármacos , Gelatina/química , Umidade , Luz , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Nanotubos/ultraestrutura , Nitrogênio/química , Porosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Staphylococcus aureus/efeitos dos fármacos , Temperatura , Resistência à Tração , Termogravimetria , Água/química , Difração de Raios X
10.
Nat Commun ; 12(1): 4393, 2021 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-34285204

RESUMO

Creating artificial macromolecular transport systems that can support the movement of molecules along defined routes is a key goal of nanotechnology. Here, we report the bottom-up construction of a macromolecular transport system in which molecular pistons diffusively move through micrometer-long, hollow filaments. The pistons can cover micrometer distances in fractions of seconds. We build the system using multi-layer DNA origami and analyze the structures of the components using transmission electron microscopy. We study the motion of the pistons along the tubes using single-molecule fluorescence microscopy and perform Langevin simulations to reveal details of the free energy surface that directs the motions of the pistons. The tubular transport system achieves diffusivities and displacement ranges known from natural molecular motors and realizes mobility improvements over five orders of magnitude compared to previous artificial random walker designs. Electric fields can also be employed to actively pull the pistons along the filaments, thereby realizing a nanoscale electric rail system. Our system presents a platform for artificial motors that move autonomously driven by chemical fuels and for performing nanotribology studies, and it could form a basis for future molecular transportation networks.


Assuntos
DNA/química , Movimento (Física) , Nanotecnologia/métodos , Nanotubos/química , DNA/ultraestrutura , Eletricidade , Cinética , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Nanotecnologia/instrumentação , Nanotubos/ultraestrutura , Propriedades de Superfície
11.
Biomed Res Int ; 2021: 9916909, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34327239

RESUMO

The fabrication of sensitive protein microarrays such as PCR used in DNA microarray is challenging due to lack of signal amplification. The development of microarrays is utilized to improve the sensitivity and limitations of detection towards primal cancer detection. The sensitivity is enhanced by the use of ZnO-nanorods and is investigated as a substrate which enhance the florescent signal to diagnose the hepatocellular carcinoma (HCC) at early stages. The substrate for deposition of ZnO-nanorods is prepared by the conventional chemical bath deposition method. The resultant highly dense ZnO-nanorods enhance the fluorescent signal 7.2 times as compared to the substrate without ZnO-nanorods. The microarray showed sensitivity of 1504.7 ng ml-1 and limit of detection of 0.1 pg ml-1 in wide dynamic range of 0.05 pg-10 µg ml-1 for alpha fetoprotein (AFP) detection in 10% human serum. This immunoassay was successfully applied for human serum samples to detect tumor marker with good recoveries. The ZnO-nanorod substrate is a simple protein microarray which showed a great promise for developing a low-cost, sensitive, and high-throughput protein assay platform for several applications in both fundamental research and clinical diagnosis.


Assuntos
Análise em Microsséries , Nanotubos/química , Soro/química , Óxido de Zinco/química , alfa-Fetoproteínas/análise , Fluorescência , Humanos , Imunoensaio , Limite de Detecção , Nanotubos/ultraestrutura , Reprodutibilidade dos Testes , Espectrometria por Raios X , Propriedades de Superfície , Fatores de Tempo , Difração de Raios X
12.
Sci Rep ; 11(1): 13266, 2021 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-34168234

RESUMO

Layered molybdenum diselenide (MoSe2) nanosheets were formed by the weak Van der Waals forces of attraction between Se and Mo atoms. MoSe2 has a larger space between the adjacent layers and smaller band gaps in the range of 0.85 to ~ 1.6 eV. In this study, MoSe2 nanosheets decorated nickel oxide (NiO) nanorods have been synthesized by hydrothermal method using sodium molybdate and selenium metal powder. NiO/MoSe2 composite formation was confirmed by powder X-ray diffraction analysis. In addition, the presence of MoSe2 nanosheets on NiO nanorods were confirmed by field emission scanning electron microscopy, high-resolution transmission electron microscopy and X-ray photoelectron spectroscopy. The Nyquist plots of NiO/MoSe2 coated glassy carbon electrode (GCE) was indicated that it had lower charge transfer resistance compared to NiO/GCE and MoSe2/GCE. Furthermore, as-prepared NiO/MoSe2/GCE was used to detect glucose in alkaline solution by cyclic voltammetry and amperometry techniques. The NiO/MoSe2/GCE was exhibited a linear response for the oxidation of glucose from 50 µM to 15.5 mM (R2 = 0.9842) at 0.5 V by amperometry. The sensor response time and the limit of detection were found to be 2 s and 0.6 µM for glucose. Moreover, selectivity of the NiO/MoSe2 sensor was tested in the presence of common interferent molecules such as hydrogen peroxide, fructose, lactose, ascorbic acid, uric acid, and dopamine. It was found that NiO/MoSe2/GCE did not respond to these interfering biomolecules. In addition, NiO/MoSe2/GCE had shown high stability, reproducibility and repeatability. Finally, the practical application of the sensor was demonstrated by detecting glucose in human blood serum with the acceptable recovery.


Assuntos
Glicemia/análise , Eletrodos , Molibdênio , Nanotubos , Níquel , Selênio , Humanos , Microscopia Eletrônica de Varredura , Nanoestruturas/ultraestrutura , Nanotubos/ultraestrutura , Espectroscopia Fotoeletrônica , Difração de Raios X
13.
Nat Commun ; 12(1): 2921, 2021 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-34012021

RESUMO

Spatial light modulators have become an essential tool for advanced microscopy, enabling breakthroughs in 3D, phase, and super-resolution imaging. However, continuous spatial-light modulation that is capable of capturing sub-millisecond microscopic motion without diffraction artifacts and polarization dependence is challenging. Here we present a photothermal spatial light modulator (PT-SLM) enabling fast phase imaging for nanoscopic 3D reconstruction. The PT-SLM can generate a step-like wavefront change, free of diffraction artifacts, with a high transmittance and a modulation efficiency independent of light polarization. We achieve a phase-shift > π and a response time as short as 70 µs with a theoretical limit in the sub microsecond range. We used the PT-SLM to perform quantitative phase imaging of sub-diffractional species to decipher the 3D nanoscopic displacement of microtubules and study the trajectory of a diffusive microtubule-associated protein, providing insights into the mechanism of protein navigation through a complex microtubule network.


Assuntos
Microscopia de Contraste de Fase/métodos , Proteínas de Ciclo Celular/metabolismo , Simulação por Computador , Ouro , Humanos , Imageamento Tridimensional/métodos , Imageamento Tridimensional/estatística & dados numéricos , Luz , Nanopartículas Metálicas/ultraestrutura , Microscopia de Força Atômica , Microscopia de Interferência/métodos , Microscopia de Interferência/estatística & dados numéricos , Microscopia de Contraste de Fase/estatística & dados numéricos , Proteínas Associadas aos Microtúbulos/metabolismo , Microtúbulos/metabolismo , Microtúbulos/ultraestrutura , Nanotecnologia , Nanotubos/ultraestrutura , Fenômenos Ópticos , Proteínas de Schizosaccharomyces pombe/metabolismo , Fatores de Tempo , Tubulina (Proteína)/metabolismo
14.
Int J Nanomedicine ; 16: 2789-2801, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33880024

RESUMO

OBJECTIVE: Gold nanorods (AuNRs) show great potential for versatile biomedical applications, such as stem cell therapy and bone tissue engineering. However, as an indispensable shape-directing agent for the growth of AuNRs, cetyltrimethylammonium bromide (CTAB) is not optimal for biological studies because it forms a cytotoxic bilayer on the AuNR surface, which interferes with the interactions with biological cells. METHODS: Citrate-stabilized AuNRs with various aspect-ratios (Cit-NRI, Cit-NRII, and Cit-NRIII) were prepared by the combination of end-selective etching and poly(sodium 4-styrenesulfonate)-assisted ligand exchange method. Their effects on osteogenic differentiation of the pre-osteoblastic cell line (MC3T3-E1), rat bone marrow mesenchymal stem cells (rBMSCs), and human periodontal ligament progenitor cells (PDLPs) have been investigated. Potential signaling pathway of citrate-stabilized AuNRs-induced osteogenic effects was also investigated. RESULTS: The experimental results showed that citrate-stabilized AuNRs have superior biocompatibility and undergo aspect-ratio-dependent osteogenic differentiation via expression of osteogenic marker genes, alkaline phosphatase (ALP) activity and formation of mineralized nodule. Furthermore, Wnt/ß-catenin signaling pathway might provide a potential explanation for the citrate-stabilized AuNRs-mediated osteogenic differentiation. CONCLUSION: These findings revealed that citrate-stabilized AuNRs with great biocompatibility could regulate the osteogenic differentiation of multiple cell types through Wnt/ß-catenin signaling pathway, which promote innovative AuNRs in the field of tissue engineering and other biomedical applications.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Ácido Cítrico/farmacologia , Ouro/farmacologia , Nanotubos/química , Osteogênese/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Células Cultivadas , Cetrimônio/farmacologia , Endocitose/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Nanotubos/ultraestrutura , Osteogênese/genética , Ligamento Periodontal/citologia , Ratos , Tiazolidinas/farmacologia , Via de Sinalização Wnt/efeitos dos fármacos
15.
Molecules ; 26(4)2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33669712

RESUMO

Hydroxyapatite (HA) is the main inorganic mineral that constitutes bone matrix and represents the most used biomaterial for bone regeneration. Over the years, it has been demonstrated that HA exhibits good biocompatibility, osteoconductivity, and osteoinductivity both in vitro and in vivo, and can be prepared by synthetic and natural sources via easy fabrication strategies. However, its low antibacterial property and its fragile nature restricts its usage for bone graft applications. In this study we functionalized a MgHA scaffold with gold nanorods (AuNRs) and evaluated its antibacterial effect against S. aureus and E. coli in both suspension and adhesion and its cytotoxicity over time (1 to 24 days). Results show that the AuNRs nano-functionalization improves the antibacterial activity with 100% bacterial reduction after 24 h. The toxicity study, however, indicates a 4.38-fold cell number decrease at 24 days. Although further optimization on nano-functionalization process are needed for cytotoxicity, these data indicated that Au-NRs nano-functionalization is a very promising method for improving the antibacterial properties of HA.


Assuntos
Anti-Infecciosos/farmacologia , Durapatita/farmacologia , Ouro/farmacologia , Magnésio/farmacologia , Nanotubos/química , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Nanotubos/ultraestrutura , Espectroscopia Fotoeletrônica , Staphylococcus aureus/efeitos dos fármacos , Tecidos Suporte/química
16.
Molecules ; 26(4)2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33670610

RESUMO

This paper presents a facile and low-cost strategy for fabrication lysozyme-loaded mesoporous silica nanotubes (MSNTs) by using silk fibroin (SF) nanofiber templates. The "top-down method" was adopted to dissolve degummed silk in CaCl2/ formic acid (FA) solvent, and the solution containing SF nanofibrils was used for electrospinning to prepare SF nanofiber templates. As SF contains a large number of -OH, -NH2 and -COOH groups, the silica layer could be easily formed on its surface by the Söber sol-gel method without adding any surfactant or coupling agent. After calcination, the MSNTs were obtained with inner diameters about 200 nm, the wall thickness ranges from 37 ± 2 nm to 66 ± 3 nm and the Brunauer-Emmett-Teller (BET) specific surface area was up to 200.48 m2/g, the pore volume was 1.109 cm3/g. By loading lysozyme, the MSNTs exhibited relatively high drug encapsulation efficiency up to 31.82% and an excellent long-term sustained release in 360 h (15 days). These results suggest that the MSNTs with the hierarchical structure of mesoporous and macroporous will be a promising carrier for applications in biomacromolecular drug delivery systems.


Assuntos
Fibroínas/química , Muramidase/metabolismo , Nanofibras/química , Nanotubos/química , Dióxido de Silício/química , Cloreto de Cálcio/química , Liberação Controlada de Fármacos , Formiatos/química , Nanofibras/ultraestrutura , Nanotubos/ultraestrutura , Porosidade , Silanos/química , Soluções , Espectrometria por Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura , Termogravimetria , Viscosidade
17.
ACS Appl Mater Interfaces ; 13(11): 12997-13008, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33719410

RESUMO

As a model radio-photodynamic therapy (RPDT) agent, we developed a multicomponent nanomaterial by anchoring conjugated chromophores on the surface of scintillating chrysotile nanotubes. Its ultimate composition makes the system a scintillation-activated photosensitizer for the singlet oxygen production. This nanomaterial shows a remarkable ability to enhance the production of singlet oxygen in an aqueous environment, under X-ray irradiation, boosting its production by almost 1 order of magnitude. Its efficiency as a coadjutant for radiotherapy has been tested in vitro, showing a striking efficacy in enhancing both the prompt cytotoxicity of the ionizing radiation and the long-term cytotoxicity given by radiation-activated apoptosis. Notably, the beneficial activity of the RPDT agent is prominent at low levels of delivered doses comparable to the one employed in clinical treatments. This opens the possibility of effectively reducing the therapy exposure and consequently undesired collateral effects due to prolonged exposure of patients to high-energy radiation.


Assuntos
Nanotubos , Neoplasias/terapia , Fármacos Fotossensibilizantes/farmacologia , Asbestos Serpentinas/química , Linhagem Celular Tumoral , Humanos , Nanotubos/química , Nanotubos/ultraestrutura , Neoplasias/metabolismo , Neoplasias/radioterapia , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Oxigênio Singlete/metabolismo , Raios X
18.
Front Immunol ; 12: 620734, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679763

RESUMO

Actin-based tunneling nanotubes are a means of intercellular communication between remote cells. In the last decade, this type of nanotube was described in a wide variety of cell types and it became widely accepted that communication through these nanotubes is related to response to environmental changes. Few reports, however, are available regarding the expression of similar nanotubes in vivo or in primary cells. Moreover, the functional significance of this intercellular communication for health and disease is largely unknown. In this context, and as a first step in unraveling these questions, we examined the formation of similar nanotubes in primary peripheral human monocytes. To that end, we combined the use of a live cell imaging system along with advanced methods of fluorescent and scanning electron microscopy. This experimental approach reveals for the first time that the bacterial lipopolysaccharide endotoxin induces a transient expression of an unexpected abundance of actin-based tunneling nanotubes associated with vesicles. In addition, it was found that a similar response can be achieved by treating human monocytes with various bacterial and yeast membrane components, as well as with a viral component analog. In all these cases, this response is mediated by distinct complexes of toll-like receptors. Therefore, we suggest that the observed phenomena are related to a broad type of monocyte pathogen response, and raise the possibility that the phenomena described above may be involved in many clinical situations related to inflammation as a new topic of study.


Assuntos
Actinas/metabolismo , Espaço Extracelular/metabolismo , Monócitos/fisiologia , Nanotubos/ultraestrutura , Comunicação Celular , Células Cultivadas , Humanos , Imunidade Inata , Lipopolissacarídeos/imunologia , Microscopia Eletrônica de Varredura , Padrões Moleculares Associados a Patógenos/imunologia , Receptores Toll-Like/metabolismo
19.
ACS Appl Mater Interfaces ; 13(11): 12972-12981, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33689269

RESUMO

Effective isolation and removal of target tumor cells from patients' peripheral blood are of great importance to clinical prognosis and recovery. However, the extremely low quantity of target cells in peripheral blood becomes one of the challenges in this respect. Herein, we design and synthesize an innovative nanostructure based on magnetic TiO2 nanotubes with Pt nanoparticles' asymmetrical decoration for effectively capturing and inactivating target cells. Using CCRF-CEM as the model cell, the resulting nanotubes with accurate modification of recognition probes exhibit high selectivity and cell-isolation efficiency upon real blood samples. Particularly, the target cells are selectively captured at a low concentration with a recovery rate of 73.0 ± 11.5% at five cells per milliliter for whole blood samples. Consequently, benefitting from the remarkable photocatalytic activity of the Janus nanotubes, these isolated cells can be rapidly inactivated via light-emitting diode (LED) irradiation with an ignorable effect on normal cells. This work offers a new paradigm for high-efficient isolating/killing target cells from a complex medium.


Assuntos
Separação Celular/métodos , Nanopartículas Metálicas/química , Nanotubos/química , Células Neoplásicas Circulantes/patologia , Titânio/química , Catálise , Linhagem Celular Tumoral , Células Endoteliais da Veia Umbilical Humana , Humanos , Nanopartículas Magnéticas de Óxido de Ferro/química , Nanotubos/ultraestrutura , Neoplasias/sangue , Processos Fotoquímicos , Platina/química
20.
Int J Nanomedicine ; 16: 2219-2236, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33762822

RESUMO

INTRODUCTION: In this paper, we have designed and formulated, a novel synthesis of doxorubicin (DOX) loaded bimetallic gold nanorods in which gold salt (HAuCl4) is chelated with anthracycline (DOX), diacid polyethylene-glycol (PEG-COOH) and gadolinium salt (GdCl3 * 6 H2O) to form DOX IN-Gd-AuNRs compared with DOX ON-Gd-AuNRs in which the drug was grafted onto the bimetallic pegylated nanoparticle surface by electrostatic adsorption. MATERIAL AND METHOD: The physical and chemical evaluation was performed by spectroscopic analytical techniques (Raman spectroscopy, UV-Visible and transmission electron microscopy (TEM)). Magnetic features at 7T were also measured. Photothermal abilities were assessed. Cytotoxicity studies on MIA PaCa-2, human pancreatic carcinoma and TIB-75 hepatocytes cell lines were carried out to evaluate their biocompatibility and showed a 320 fold higher efficiency for DOX after encapsulation. RESULTS: Exhaustive physicochemical characterization studies were conducted showing a mid size of 20 to 40 nm diameters obtained with low polydispersity, efficient synthesis using seed mediated synthesis with chelation reaction with high scale-up, long duration stability, specific doxorubicin release with acidic pH, strong photothermal abilities at 808 nm in the NIR transparency window, strong magnetic r1 relaxivities for positive MRI, well adapted for image guided therapy and therapeutical purpose in biological tissues. CONCLUSION: In this paper, we have developed a novel theranostic nanoparticle composed of gadolinium complexes to gold ions, with a PEG biopolymer matrix conjugated with antitumoral doxorubicin, providing multifunctional therapeutic features. Particularly, these nano conjugates enhanced the cytotoxicity toward tumoral MIAPaCa-2 cells by a factor of 320 compared to doxorubicin alone. Moreover, MRI T1 features at 7T enables interesting positive contrast for bioimaging and their adapted size for potential passive targeting to tumors by Enhanced Permeability Retention. Given these encouraging antitumoral and imaging properties, this bimetallic theranostic nanomaterial system represents a veritable promise as a therapeutic entity in the field of medicinal applications.


Assuntos
Doxorrubicina/uso terapêutico , Gadolínio/química , Ouro/química , Nanotubos/química , Nanomedicina Teranóstica , Animais , Antibióticos Antineoplásicos/farmacologia , Antibióticos Antineoplásicos/uso terapêutico , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Liberação Controlada de Fármacos , Endocitose , Humanos , Concentração Inibidora 50 , Imageamento por Ressonância Magnética , Camundongos , Nanotubos/ultraestrutura , Neoplasias/tratamento farmacológico , Terapia Fototérmica , Espectrofotometria Ultravioleta
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