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1.
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
2.
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
3.
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 , Imagem por Ressonância Magnética , Camundongos , Nanotubos/ultraestrutura , Neoplasias/tratamento farmacológico , Espectrofotometria Ultravioleta
4.
Int J Nanomedicine ; 16: 667-682, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33531806

RESUMO

Background: Nanostructured surface modifications of Ti-based biomaterials are moving up from a highly-promising to a successfully-implemented approach to developing safe and reliable implants. Methods: The study's main objective is to help consolidate the knowledge and identify the more suitable experimental strategies related to TiO2 nanotubes-modified surfaces. In this sense, it proposes the thorough investigation of two optimized nanotubes morphologies in terms of their biological activity (cell cytotoxicity, alkaline phosphatase activity, alizarin red mineralization test, and cellular adhesion) and their electrochemical behavior in simulated body fluid (SBF) electrolyte. Layers of small-short and large-long nanotubes were prepared and investigated in their amorphous and crystallized states and compared to non-anodized samples. Results: Results show that much more than the surface area development associated with the nanotubes' growth; it is the heat treatment-induced change from amorphous to crystalline anatase-rutile structures that ensure enhanced biological activity coupled to high corrosion resistance. Conclusion: Compared to both non-anodized and amorphous nanotubes layers, the crystallized nano-structures' outstanding bioactivity was related to the remarkable increase in their hydrophilic behavior, while the enhanced electrochemical stability was ascribed to the thickening of the dense rutile barrier layer at the Ti surface beneath the nanotubes.


Assuntos
Nanotubos/química , Próteses e Implantes , Titânio/química , Fosfatase Alcalina/metabolismo , Adesão Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Corrosão , Eletroquímica , Eletrólitos/química , Humanos , Nanotubos/ultraestrutura , Molhabilidade
5.
ACS Appl Mater Interfaces ; 13(4): 5795-5802, 2021 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-33480669

RESUMO

A novel ratiometric electrochemical (EC) sensing platform was established for sensitive immunoassay of target cytokeratin 19 fragment 21-1 (CYFRA21-1) biomarker by combining competitive immunoreaction and multisignal output. This immunosensor utilized Ag nanoparticles (NPs)-functionalized urchin-like Fe3O4@polydopamine (u-Fe3O4@PDA-Ag) as a matrix to immobilize CYFRA21-1 antigens and methylene blue (MB)-absorbed Ni3Si2O5(OH)4-Au nanotubes (NTs) to label the anti-CYFRA21-1 (Ab). During the competitive immunoreaction, square wave voltammetric (SWV) current changes of Ag NPs from u-Fe3O4@PDA-Ag indicator and MB from Ni3Si2O5(OH)4-Au/MB indicator are relevant to the dosage of CYFRA21-1-acquired Ni3Si2O5(OH)4-Au/MB/Ab. More importantly, numerous CYFRA21-1 loaded stably on u-Fe3O4@PDA-Ag exhibited strong competitive capacity toward the target-CYFRA21-1 to combine Ni3Si2O5(OH)4-Au/MB/Ab, causing sensitive changes in the ratio of two measured SWV currents. Prominently, "ΔI = ΔIMB + |ΔIAg NPs|" (ΔIMB and |ΔIAg NPs| represents the change values of the oxidation peak currents of MB and Ag NPs, respectively) could be regarded as significantly amplifying the signal response and ultimately improving the sensitivity of CYFRA21-1 detection, from which we derived a wide dynamic range from 500 fg/mL to 50 ng/mL and a low detection limit of 0.39 pg/mL (S/N = 3). This work may exert a profound impact on monitoring other biomarkers in early diagnosis of diseases.


Assuntos
Antígenos de Neoplasias/sangue , Óxido Ferroso-Férrico/química , Ouro/química , Queratina-19/sangue , Azul de Metileno/química , Nanotubos/química , Antígenos de Neoplasias/análise , Técnicas Eletroquímicas/métodos , Humanos , Imunoensaio/métodos , Indóis/química , Queratina-19/análise , Limite de Detecção , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Nanotubos/ultraestrutura , Polímeros/química , Compostos de Silício/química , Prata/química
6.
Carbohydr Polym ; 254: 117465, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357924

RESUMO

Designing multifunctional surfaces is key to develop advanced materials for orthopedic applications. In this study, we design a double-layer coating, assembled onto the completely regular titania nanotubes (cRTNT) array. Benefiting from the biological and topological characteristics of chitosan nanofibers (CH) and reduced graphene oxide (RGO) through a unique assembly, the designed material features promoted osteoblast cell viability, prolonged antibiotic release profile, as well as inhibited bacterial biofilm formation. The synergistic effect of RGO and CH on the biological performance of the surface is investigatSed. The unique morphology of the nanofibers leads to the partial coverage of RGO-modified nanotubes, providing an opportunity to access the sublayer properties. Another merit of this coating lies in its morphological similarity to the extracellular matrix (ECM) to boost cellular performance. According to the results of this study, this platform holds promising advantages over the bare and bulk biopolymer-modified TNTs.


Assuntos
Quitosana/síntese química , Materiais Revestidos Biocompatíveis/química , Grafite/química , Nanocompostos/química , Osteoblastos/efeitos dos fármacos , Titânio/química , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Adesão Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Materiais Revestidos Biocompatíveis/farmacologia , Portadores de Fármacos , Liberação Controlada de Fármacos , Humanos , Cinética , Nanocompostos/ultraestrutura , Nanotubos/química , Nanotubos/ultraestrutura , Osteoblastos/citologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/crescimento & desenvolvimento , Vancomicina/farmacologia
7.
Biochem Biophys Res Commun ; 535: 33-38, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33340763

RESUMO

Nano titanium implants induce osteogenesis, but how osteoblasts respond to this physical stimulation remains unclear. In this study, we tried to reveal the role of the mitochondrial fission-fusion of osteoblasts in response to a nano titanium surface during the process of osteogenesis, which is important for the design of the surface structure of titanium implants. A TiO2 nanotube array (nano titanium, NT) was fabricated by anodization, and a smooth surface (smooth titanium, ST) was used as a control. We investigated changes in the mitochondrial fission-fusion (MFF) dynamics in MC3T3-E1 cells on the NT surface with those on the ST surface by performing transmission electron microscopy (TEM), confocal laser scanning microscope (CLSM) and real-time PCR. At the same time, we also detected changes in the MFF and osteogenic differentiation of MC3T3-E1 cells after DRP1 downregulation with RNA interference. Cells on the NT surface exhibited more mitochondrial fusion than those on the ST surface, and DRP1 was the key regulatory molecule. Interestingly, DRP1 increased for only a short time at the early stage on the NT surface, and when DRP1 was inhibited by siRNA at the early stage, the osteogenic differentiation of MC3T3-E1 cells significantly decreased. In conclusion, DRP1-regulated mitochondrial dynamics played a key role in the nanotopography-accelerated osteogenic differentiation of MC3T3-E1 cells.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Dinâmica Mitocondrial/efeitos dos fármacos , Nanotubos/toxicidade , Osteogênese/efeitos dos fármacos , Titânio/toxicidade , Animais , Diferenciação Celular/genética , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Dinaminas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Camundongos , Dinâmica Mitocondrial/genética , Nanotubos/ultraestrutura , Osteogênese/genética , Propriedades de Superfície
8.
Int J Mol Sci ; 22(1)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33374960

RESUMO

To increase the efficiency of therapy via enhancing its selectivity, the usage of gold nanorods (GNR) as a factor sensitizing cancer cells to radiation was proposed. Due to gold nanoparticles' characteristics, the smaller doses of radiation would be sufficient in the treatment, protecting the healthy tissue around the tumor. The aim of this study was to investigate the effect of gold nanorods on cancer and normal prostate cells and the role of nanorods in the cell response to ionizing radiation. The effect was evaluated by measuring the toxicity, cell cycle, cell granularity, reactive oxygen species (ROS) level, and survival fractions. Nanorods showed a strong toxicity dependent on the concentration and incubation time toward all used cell lines. A slight effect of nanorods on the cycle distribution was observed. The results demonstrated that the administration of nanorods at higher concentrations resulted in an increased level of generated radicals. The results of cellular proliferation after irradiation are ambiguous; however, there are noticeable differences after the application of nanorods before irradiation. The obtained results lead to the conclusion that nanorods affect the physiology of both normal and cancer cells. Nanorods might become a potential tool used to increase the effectiveness of radiation treatment.


Assuntos
Ouro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Radiação Ionizante , Radiossensibilizantes/administração & dosagem , Ciclo Celular/efeitos dos fármacos , Ciclo Celular/efeitos da radiação , Linhagem Celular , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Relação Dose-Resposta a Droga , Relação Dose-Resposta à Radiação , Ouro/química , Humanos , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Microscopia Eletrônica de Transmissão , Nanotubos/química , Nanotubos/ultraestrutura , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Radiossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Fatores de Tempo
9.
Int J Nanomedicine ; 15: 4471-4481, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606689

RESUMO

Background: Ineffective integration has been recognized as one of the major causes of early orthopedic failure of titanium-based implants. One strategy to address this problem is to develop modified titanium surfaces that promote osteoblast differentiation. This study explored titanium surfaces modified with TiO2 nanotubes (TiO2 NTs) capable of localized drug delivery into bone and enhanced osteoblast cell differentiation. Materials and Methods: Briefly, TiO2 NTs were subjected to anodic oxidation and loaded with Metformin, a widely used diabetes drug. To create surfaces with sustainable drug-eluting characteristics, TiO2 NTs were spin coated with a thin layer of chitosan. The surfaces were characterized via scanning electron microscopy, atomic force microscopy, and contact angle measurements. The surfaces were then exposed to mesenchymal bone marrow stem cells (MSCs) to evaluate cell adhesion, growth, differentiation, and morphology on the modified surfaces. Results: A noticeable increase in drug release time (3 days vs 20 days) and a decrease in burst release characteristics (85% to 7%) was observed in coated samples as compared to uncoated samples, respectively. Chitosan-coated TiO2 NTs exhibited a considerable enhancement in cell adhesion, proliferation, and genetic expression of type I collagen, and alkaline phosphatase activity as compared to uncoated TiO2 NTs. Conclusion: TiO2 NT surfaces with a chitosan coating are capable of delivering Metformin to a bone site over a sustained period of time with the potential to enhance MSCs cell attachment, proliferation, and differentiation.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Quitosana/química , Liberação Controlada de Fármacos , Metformina/farmacologia , Nanotubos/química , Osteoblastos/citologia , Titânio/química , Fosfatase Alcalina/metabolismo , Animais , Adesão Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Nanotubos/ultraestrutura , Osteoblastos/efeitos dos fármacos , Osteoblastos/ultraestrutura , Osteogênese/efeitos dos fármacos , Ratos Wistar , Molhabilidade
10.
Life Sci ; 257: 118108, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32682920

RESUMO

AIM: Preparation of pegylated gold nanorods (PEG-AuNRs) that are capable of converting near infrared (NIR) light into heat. Evaluation of cancer therapeutic efficacy and long-term toxicity of the proposed photothermal therapy in comparison with other conventional modalities. MATERIALS AND METHODS: Prepared PEG-AuNRs were characterized by measuring their absorption spectra, zeta potential, and transmission electron microscope (TEM). Cancer therapeutic efficacy was assessed by monitoring tumor growth, measuring DNA damage and superoxide dismutase (SOD) and malondialdehyde (MDA) levels in addition to examining tumor histopathology. Further analysis concerning the toxicity of all the proposed treatment modalities was also assessed by evaluating the cytotoxicity and genotoxicity in liver and kidney tissues. KEY FINDINGS: The results demonstrated that both photothermal therapy (PEG-AuNRs + NIR laser) and chemotherapy (cisplatin) have higher efficacy in diminishing Ehrlich tumor growth with significance DNA damage over the other treatment modalities. Concerning the biosafety issue, mice treated photothermally exhibited lower MDA level and higher SOD activity in liver and kidney tissues compared with other treated groups. DNA damage represented by tail moment and olive moment of kidney tissues exhibited lower values for photothermal treated group and higher values for cisplatin treated group. SIGNIFICANCE: Photothermal therapy (PEG-AuNRs + NIR laser) potentiates higher efficacy in treating Ehrlich tumor with minimum toxicity in comparison with other conventional treatment modalities.


Assuntos
Carcinoma de Ehrlich/terapia , Ouro/administração & dosagem , Nanotubos/toxicidade , Fototerapia/métodos , Animais , Carcinoma de Ehrlich/patologia , Ensaio Cometa , Dano ao DNA/efeitos dos fármacos , Feminino , Ouro/uso terapêutico , Ouro/toxicidade , Malondialdeído/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica de Transmissão , Nanotubos/ultraestrutura , Transplante de Neoplasias , Estresse Oxidativo , Superóxido Dismutase/metabolismo
11.
J Vis Exp ; (159)2020 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-32449715

RESUMO

A biomimetic NM was developed to serve as a tissue-engineering biological scaffold, which can enhance stem cell anchorage. The biomimetic NM is formed from JBNTs and FN through self-assembly in an aqueous solution. JBNTs measure 200-300 µm in length with inner hydrophobic hollow channels and outer hydrophilic surfaces. JBNTs are positively charged and FNs are negatively charged. Therefore, when injected into a neutral aqueous solution, they are bonded together via noncovalent bonding to form the NM bundles. The self-assembly process is completed within a few seconds without any chemical initiators, heat source, or UV light. When the pH of the NM solution is lower than the isoelectric point of FNs (pI 5.5-6.0), the NM bundles will self-release due to the presence of positively charged FN. NM is known to mimic the extracellular matrix (ECM) morphologically and hence, can be used as an injectable scaffold, which provides an excellent platform to enhance hMSC adhesion. Cell density analysis and fluorescence imaging experiments indicated that the NMs significantly increased the anchorage of hMSCs compared to the negative control.


Assuntos
Biomimética/métodos , Matriz Extracelular/metabolismo , Fibronectinas/farmacologia , Células-Tronco Mesenquimais/citologia , Nanotubos/química , Adesão Celular/efeitos dos fármacos , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/ultraestrutura , Fluorescência , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/ultraestrutura , Nanotubos/ultraestrutura
12.
Nat Commun ; 11(1): 2495, 2020 05 19.
Artigo em Inglês | MEDLINE | ID: mdl-32427872

RESUMO

Colloidal crystal engineering with nucleic acid-modified nanoparticles is a powerful way for preparing 3D superlattices, which may be useful in many areas, including catalysis, sensing, and photonics. To date, the building blocks studied have been primarily based upon metals, metal oxides, chalcogenide semiconductors, and proteins. Here, we show that metal-organic framework nanoparticles (MOF NPs) densely functionalized with oligonucleotides can be programmed to crystallize into a diverse set of superlattices with well-defined crystal symmetries and compositions. Electron microscopy and small-angle X-ray scattering characterization confirm the formation of single-component MOF superlattices, binary MOF-Au single crystals, and two-dimensional MOF nanorod assemblies. Importantly, DNA-modified porphyrinic MOF nanorods (PCN-222) were assembled into 2D superlattices and found to be catalytically active for the photooxidation of 2-chloroethyl ethyl sulfide (CEES, a chemical warfare simulant of mustard gas). Taken together, these new materials and methods provide access to colloidal crystals that incorporate particles with the well-established designer properties of MOFs and, therefore, increase the scope of possibilities for colloidal crystal engineering with DNA.


Assuntos
Coloides/química , DNA/química , Estruturas Metalorgânicas/química , Nanopartículas/química , Cristalização , DNA/genética , Engenharia/métodos , Microscopia Eletrônica de Transmissão e Varredura/métodos , Nanopartículas/ultraestrutura , Nanotubos/química , Nanotubos/ultraestrutura , Tamanho da Partícula , Espalhamento a Baixo Ângulo , Prata/química , Difração de Raios X
13.
Int J Nanomedicine ; 15: 2541-2553, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32368039

RESUMO

Background: In the emerging field of nanotechnology, copper oxide (CuO) nanomaterials are considered to be one of the most important transition metal oxides owing to its fascinating properties. Its synthesis from green chemistry principles is gaining importance as next-generation antibiotics due to its simplicity, eco-friendliness, and cost-effectiveness. In the present study, CuO nanorods (CuO NRs) were synthesized from the aqueous fruit extract of Momordica charantia and characterized using different analytical techniques. Further, the biomedical therapeutic potential was evaluated against multi-drug resistant microbial strains. Materials and Methods: To synthesize CuO NRs, 0.1M of CuSO4.5H2O solution was added to aqueous extract of Momordica charantia in a 1:3 (v/v) ratio (pH=11) and heated at 50°C followed by washing and drying. The synthesized CuO NRs were subjected to characterization using different analytical techniques such as UV visible spectroscopy, zeta sizer equipped with zeta potential, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), scanning electron microscopy (SEM) equipped with energy-dispersive X-ray spectroscopy (EDS) and transmission electron microscopy (TEM). Further, the application as a biomedical therapeutic potential was evaluated in vitro using well diffusion method against eleven multidrug-resistant clinical bacterial strains, a fungus- Trichophyton rubrum and in ovo against the R2B virus using haemagglutination (HA) test. Results: Characterization was preliminarily done by the spectral study that confirms the absorbance band at 245nm. FTIR analysis at 628 cm-1 peak identified copper oxide vibration. SEM analysis revealed agglomerated particle clusters. However, with TEM clear nanorods of average diameter of 61.48 ± 2 nm were observed. EDAX confirmed CuO formation while XRD showed a typical monoclinic structure with 6 nm crystallite size. Biological screening of CuO NRs showed significant results against both in vitro and in ovo methods. Significant inhibitory activity (p<0.0001) was noted against most of the resistant human pathogenic strains including both Gram-positive and Gram-negative bacteria. The highest efficacy was observed against Bacillus cereus with a 31.66 mm zone of inhibition. Besides, the therapeutic potential of CuO NRs against Corynebacterium xerosis, Streptococcus viridians and R2B strain of Newcastle disease is reported for the first time. Conclusion: Based on the present results, it could be expected that green synthesized CuO NRs would find potential applications in the field of nanomedicine.


Assuntos
Antibacterianos/farmacologia , Cobre/farmacologia , Química Verde , Momordica charantia/química , Nanoestruturas/química , Animais , Antifúngicos/farmacologia , Bactérias/efeitos dos fármacos , Galinhas , Fungos/efeitos dos fármacos , Testes de Hemaglutinação , Humanos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Testes de Sensibilidade Microbiana , Nanoestruturas/ultraestrutura , Nanotubos/química , Nanotubos/ultraestrutura , Tamanho da Partícula , Espectrometria por Raios X , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier , Eletricidade Estática , Difração de Raios X
14.
Int J Nanomedicine ; 15: 2151-2169, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32280212

RESUMO

Introduction: In recent years there has been ample interest in nanoscale modifications of synthetic biomaterials to understand fundamental aspects of cell-surface interactions towards improved biological outcomes. In this study, we aimed at closing in on the effects of nanotubular TiO2 surfaces with variable nanotopography on the response on human mesenchymal stem cells (hMSCs). Although the influence of TiO2 nanotubes on the cellular response, and in particular on hMSC activity, has already been addressed in the past, previous studies overlooked critical morphological, structural and physical aspects that go beyond the simple nanotube diameter, such as spatial statistics. Methods: To bridge this gap, we implemented an extensive characterization of nanotubular surfaces generated by anodization of titanium with a focus on spatial structural variables including eccentricity, nearest neighbour distance (NND) and Voronoi entropy, and associated them to the hMSC response. In addition, we assessed the biological potential of a two-tiered honeycomb nanoarchitecture, which allowed the detection of combinatory effects that this hierarchical structure has on stem cells with respect to conventional nanotubular designs. We have combined experimental techniques, ranging from Scanning Electron (SEM) and Atomic Force (AFM) microscopy to Raman spectroscopy, with computational simulations to characterize and model nanotubular surfaces. We evaluated the cell response at 6 hrs, 1 and 2 days by fluorescence microscopy, as well as bone mineral deposition by Raman spectroscopy, demonstrating substrate-induced differential biological cueing at both the short- and long-term. Results: Our work demonstrates that the nanotube diameter is not sufficient to comprehensively characterize nanotubular surfaces and equally important parameters, such as eccentricity and wall thickness, ought to be included since they all contribute to the overall spatial disorder which, in turn, dictates the overall bioactive potential. We have also demonstrated that nanotubular surfaces affect the quality of bone mineral deposited by differentiated stem cells. Lastly, we closed in on the integrated effects exerted by the superimposition of two dissimilar nanotubular arrays in the honeycomb architecture. Discussion: This work delineates a novel approach for the characterization of TiO2 nanotubes which supports the incorporation of critical spatial structural aspects that have been overlooked in previous research. This is a crucial aspect to interpret cellular behaviour on nanotubular substrates. Consequently, we anticipate that this strategy will contribute to the unification of studies focused on the use of such powerful nanostructured surfaces not only for biomedical applications but also in other technology fields, such as catalysis.


Assuntos
Células-Tronco Mesenquimais/citologia , Nanotubos/química , Estatística como Assunto , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Adesões Focais/efeitos dos fármacos , Adesões Focais/metabolismo , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Minerais/análise , Nanotubos/ultraestrutura , Fator de Transcrição Sp7/metabolismo , Propriedades de Superfície , Titânio/química
15.
Sensors (Basel) ; 20(3)2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32050725

RESUMO

There has been growing interest in using strong field enhancement and light localization in plasmonic nanostructures to control the polarization properties of light. Various experimental techniques are now used to fabricate twisted metallic nanoparticles and metasurfaces, where strongly enhanced chiral near-fields are used to intensify circular dichroism (CD) signals. In this review, state-of-the-art strategies to develop such chiral plasmonic nanoparticles and metasurfaces are summarized, with emphasis on the most recent trends for the design and development of functionalizable surfaces. The major objective is to perform enantiomer selection which is relevant in pharmaceutical applications and for biosensing. Enhanced sensing capabilities are key for the design and manufacture of lab-on-a-chip devices, commonly named point-of-care biosensing devices, which are promising for next-generation healthcare systems.


Assuntos
Técnicas Biossensoriais , Sistemas Automatizados de Assistência Junto ao Leito , DNA/química , Eletricidade , Ouro/química , Imageamento Tridimensional , Bicamadas Lipídicas/química , Nanoestruturas/química , Nanotubos/química , Nanotubos/ultraestrutura , Pontos Quânticos/química , Estereoisomerismo , Água/química
16.
Nanoscale ; 12(6): 4159-4166, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32022812

RESUMO

Thrombin aptamers (TBAs) have attracted much attention due to their various applications. The structures and properties of long ssDNA chains with multiple TBA repeat sequences are interesting and distinct from those of their monomers. Due to the complexity of the sample system, it is quite difficult to reveal the structure of such a long-chain ssDNA using traditional methods. In this work, we investigated the repeated ssDNA by using single-molecule magnetic tweezers and AFM imaging. To do that we developed the polymerase change-rolling circle amplification (PC-RCA) synthetic method and prepared two-end modified repeated ssDNA. The rod-like G4 structures formed by intramolecular stacking of the repeat sequence were for the first time identified. This novel structure is different from those higher-order quadruplex structures formed by G-tetrads or loop-mediated interactions. It is also quite interesting to find that the increase of the TBA copy number can unitize the diversity of TBA conformation to the best-fit binding structure for thrombin. The methodology developed in this work can be used for studying other repeat sequences in the genome, such as telomeric DNA as well as interactions of ssDNA with the binding molecule.


Assuntos
Aptâmeros de Nucleotídeos/química , DNA de Cadeia Simples/ultraestrutura , Nanotubos/ultraestrutura , Imagem Individual de Molécula/métodos , Aptâmeros de Nucleotídeos/metabolismo , DNA de Cadeia Simples/química , Quadruplex G , Nanotubos/química
17.
J Trace Elem Med Biol ; 58: 126448, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31901726

RESUMO

BACKGROUND: Increasing resistance to available drugs and their associated side-effects have drawn wide attention towards designing alternative therapeutic strategies for control of hyperglycemia and oxidative stress. The roles of the sizes and shapes of the nanomaterials used in the treatment and management of Type 2 Diabetes Mellitus (T2DM) in preventing chronic hyperglycaemia and oxidative stress are investigated. We report specifically on the effects of doping silver (Ag) into the ZnO nanorods (ZnO:Ag NR's) as a rational drug designing strategy. METHODS: Inhibition of porcine pancreatic α-amylase, murine pancreatic amylase, α-glucosidase, murine intestinal glucosidase and amyloglucosidase are checked for evaluation of antidiabetic potential. In addition, the radical scavenging activities of ZnO:Ag NR's against nitric oxide, DDPH and superoxide radicals are evaluated. RESULTS: Quantitative radical scavenging and metabolic enzyme inhibition activities of ZnO:Ag NR's at a concentration of 100 µg/mL were found to depend on the amount of Ag doped in up to a threshold level (3-4 %). Circular dichroism analysis revealed that the interaction of the NR's with the enzymes altered their secondary conformation. This alteration is the underlying mechanism for the potent enzyme inhibition. CONCLUSIONS: Enhanced inhibition of enzymes and scavenging of free radicals primarily responsible for reactive oxygen species (ROS) mediated damage, provide a strong scientific rationale for considering ZnO:Ag NR's as a candidate nanomedicine for controlling postprandial hyperglycaemia and the associated oxidative stress.


Assuntos
Antioxidantes/farmacologia , Hipoglicemiantes/farmacologia , Nanotubos/química , Prata/farmacologia , Óxido de Zinco/farmacologia , Amilases/antagonistas & inibidores , Amilases/metabolismo , Animais , Compostos de Bifenilo/química , Inibidores Enzimáticos/farmacologia , Depuradores de Radicais Livres/metabolismo , Inibidores de Glicosídeo Hidrolases/farmacologia , Intestinos/enzimologia , Camundongos , Nanotubos/ultraestrutura , Óxido Nítrico/metabolismo , Pâncreas/enzimologia , Picratos/química , Superóxidos/metabolismo , Suínos , alfa-Glucosidases/metabolismo
18.
Anal Bioanal Chem ; 412(4): 841-848, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31897553

RESUMO

A sensitive photoelectrochemical (PEC) aptasensor was constructed for prostate-specific antigen (PSA) detection using an enhanced photocurrent response strategy. The p-n heterostructure CdS-Cu2O nanorod arrays were prepared on Ti mesh (CdS-Cu2O NAs/TM) by a simple hydrothermal method and successive ionic-layer adsorption reactions. Compared with the original CdS/TM, the synergistic effect of p-n type CdS-Cu2O NAs/TM and the internal electric field realizes the effective separation of photoinduced electron-hole pairs and improves the PEC performance. In order to construct the aptasensor, an amino-modified aptamer was immobilized on CdS-Cu2O NAs/TM to serve as a recognition unit for PSA. After the introduction of PSA, PSA was specifically captured by the aptamer on the PEC aptasensor, which can be oxidized by photogenerated holes to prevent electron-hole recombination and increase photocurrent. Under optimal conditions, the constructed PEC aptasensor has a linear range of 0.1-100 ng·mL-1 and a detection limit as low as 0.026 ng·mL-1. The results of aptasensor detection of human serum indicate that it has broad application prospects in biosensors and photoelectrochemical analysis.


Assuntos
Aptâmeros de Nucleotídeos/química , Compostos de Cádmio/química , Cobre/química , Nanotubos/química , Antígeno Prostático Específico/sangue , Sulfetos/química , Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Humanos , Limite de Detecção , Nanotubos/ultraestrutura
19.
Biochem Biophys Res Commun ; 523(4): 1014-1019, 2020 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-31973818

RESUMO

Dynein motor proteins usually work as a group in vesicle transport, mitosis, and ciliary/flagellar beating inside cells. Despite the obvious importance of the functions of dynein, the effect of inter-dynein interactions on collective motility remains poorly understood due to the difficulty in building large dynein ensembles with defined geometry. Here, we describe a method to build dynein ensembles to investigate the collective motility of dynein on microtubules. Using electron microscopy, we show that tens to hundreds of cytoplasmic dynein monomers were anchored along a 4- or 10-helix DNA nanotube with an average periodicity of 19 or 44 nm (a programmed periodicity of 14 or 28 nm, respectively). They drove the sliding movement of DNA nanotubes along microtubules at a velocity of 170-620 nm/s. Reducing the stiffness of DNA nanotubes made the nanotube movement discontinuous and considerably slower. Decreasing the spacing between motors simply slowed down the nanotube movement. This slowdown was independent of the number of motors involved but heavily dependent on motor-motor distance. This suggests that steric hindrance or mechanical coupling between dynein molecules was responsible for the slowdown. Furthermore, we observed cyclical buckling of DNA nanotubes on microtubules, reminiscent of ciliary/flagellar beating. These results highlight the importance of the geometric arrangement of dynein motors on their collective motility.


Assuntos
DNA/metabolismo , Dineínas/metabolismo , Nanotubos/química , DNA/ultraestrutura , Dineínas/ultraestrutura , Humanos , Microtúbulos/metabolismo , Microtúbulos/ultraestrutura , Nanotubos/ultraestrutura , Transporte Proteico , Proteínas Recombinantes/metabolismo
20.
Lasers Med Sci ; 35(8): 1729-1740, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31965353

RESUMO

Despite of high in vitro anticancer efficacy of many chemotherapeutics, their in vivo use is limited due to lack of biocompatibility and tumor targeting. Near-infrared (NIR) photothermally induced phase transition of PLGA-PEG regime was utilized for developing highly efficient photoresponsive drug delivery systems. Co-encapsulation of plasmonic gold nanorods (GNRs), as NIR-trigger, with the novel and highly efficient anticancer drug N'-(2-Methoxybenzylidene)-3-methyl-1-phenyl-H-Thieno[2,3-c]Pyrazole-5-Carbohyd-razide (MTPC) produced NIR-responsive biodegradable polymeric (PLGA-b-PEG) nanocapsules. This remotely controllable drug release significantly enhanced both biodistribution and pharmacokinetics of the hydrophobic drug. Intravenous (IV) injection of the prepared nanocapsules (MTPC/GNRs@PLGA-PEG) to tumor-bearing mice followed by extracorporeal exposure of the tumor to NIR light resulted in highly selective drug accumulation at the tumor sites. In vivo biodistribution and pharmacokinetics utilizing iodine-131 drug-radiolabelling technique revealed a maximum target to non-target ratio (T/NT) of 5.8, 4 h post-injection with maximum drug level in the tumor (6.3 ± 0.6% of the injected dose). Graphical abstract.


Assuntos
Antineoplásicos/uso terapêutico , Ouro/química , Nanotubos/química , Polietilenoglicóis/química , Poliglactina 910/química , Espectroscopia de Luz Próxima ao Infravermelho , Animais , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Feminino , Humanos , Hidrazinas/química , Hidrazinas/farmacocinética , Hidrazinas/uso terapêutico , Radioisótopos do Iodo/química , Células MCF-7 , Camundongos , Nanocápsulas/química , Nanotubos/ultraestrutura , Distribuição Tecidual
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