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1.
Nat Commun ; 11(1): 4384, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32873796

RESUMO

The ability to detect low concentrations of biomarkers in patient samples is one of the cornerstones of modern healthcare. In general, biosensing approaches are based on measuring signals resulting from the interaction of a large ensemble of molecules with the sensor. Here, we report a biosensor platform using DNA origami featuring a central cavity with a target-specific DNA aptamer coupled with a nanopore read-out to enable individual biomarker detection. We show that the modulation of the ion current through the nanopore upon the DNA origami translocation strongly depends on the presence of the biomarker in the cavity. We exploit this to generate a biosensing platform with a limit of detection of 3 nM and capable of the detection of human C-reactive protein (CRP) in clinically relevant fluids. Future development of this approach may enable multiplexed biomarker detection by using ribbons of DNA origami with integrated barcoding.


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/instrumentação , DNA/química , Nanoestruturas/química , Imagem Individual de Molécula/instrumentação , Biomarcadores/análise , Proteína C-Reativa/análise , Desenho de Equipamento , Humanos , Limite de Detecção , Nanotecnologia/métodos
2.
J Nanobiotechnology ; 18(1): 125, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32891146

RESUMO

Incidents of viral outbreaks have increased at an alarming rate over the past decades. The most recent human coronavirus known as COVID-19 (SARS-CoV-2) has already spread around the world and shown R0 values from 2.2 to 2.68. However, the ratio between mortality and number of infections seems to be lower in this case in comparison to other human coronaviruses (such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)). These outbreaks have tested the limits of healthcare systems and have posed serious questions about management using conventional therapies and diagnostic tools. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. In this review, we discuss the use of nanotechnology for COVID-19 virus management by the development of nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and nanocarrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanotecnologia/métodos , Pandemias , Pneumonia Viral , Antivirais/administração & dosagem , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Desinfecção/métodos , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Humanos , Nanoestruturas/administração & dosagem , Equipamento de Proteção Individual , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Vacinas Virais/administração & dosagem
3.
Anal Chem ; 92(19): 13396-13404, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32867467

RESUMO

Rapid, accurate, reliable, and risk-free tracking of pathogenic microorganisms at the single-cell level is critical to achieve efficient source control and prevent outbreaks of microbial infectious diseases. For the first time, we report a promising approach for integrating the concepts of a remarkably large Stokes shift and dual-recognition into a single matrix to develop a pathogenic microorganism stimuli-responsive ratiometric fluorescent nanoprobe with speed, cost efficiency, stability, ultrahigh specificity, and sensitivity. As a proof-of-concept, we selected the Gram-positive bacterium Staphylococcus aureus (S. aureus) as the target analyte model, which easily bound to its recognition aptamer and the broad-spectrum glycopeptide antibiotic vancomycin (Van). To improve the specificity and short sample-to-answer time, we employed classic noncovalent π-π stacking interactions as a driving force to trigger the binding of Van and aptamer dual-functionalized near-infrared (NIR) fluorescent Apt-Van-QDs to the surface of an unreported blue fluorescent π-rich electronic carbon nanoparticles (CNPs), achieving S. aureus stimuli-responsive ratiometric nanoprobe Apt-Van-QDs@CNPs. In the assembly of Apt-Van-QDs@CNPs, the blue CNPs (energy donor) and NIR Apt-Van-QDs (energy acceptor) became close to allow the fluorescence resonance energy transfer (FRET) process, leading to a remarkable blue fluorescence quenching for the CNPs at ∼465 nm and a clear NIR fluorescence enhancement for Apt-Van-QDs at ∼725 nm. In the presence of S. aureus, the FRET process from CNPs to Apt-Van-QDs was disrupted, causing the nanoprobe Apt-Van-QDs@CNPs to display a ratiometric fluorescent response to S. aureus, which exhibited a large Stokes shift of ∼260 nm and rapid sample-to-answer detection time (∼30.0 min). As expected, the nanoprobe Apt-Van-QDs@CNPs showed an ultrahigh specificity for ratiometric fluorescence detection of S. aureus with a good detection limit of 1.0 CFU/mL, allowing the assay at single-cell level. Moreover, we also carried out the precise analysis of S. aureus in actual samples with acceptable results. We believe that this work offers new insight into the rational design of efficient ratiometric nanoprobes for rapid on-site accurate screening of pathogenic microorganisms at the single-cell level in the early stages, especially during the worldwide spread of COVID-19 today.


Assuntos
Bactérias/química , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/síntese química , Nanotecnologia/métodos , Antibacterianos/farmacologia , Aptâmeros de Nucleotídeos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/microbiologia , Fluorescência , Transferência Ressonante de Energia de Fluorescência , Microbiologia de Alimentos/métodos , Humanos , Nanopartículas , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/microbiologia , Sensibilidade e Especificidade , Espectroscopia de Luz Próxima ao Infravermelho , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/química , Vancomicina/farmacologia
4.
Adv Healthc Mater ; 9(19): e2000979, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32885616

RESUMO

Researchers, engineers, and medical doctors are made aware of the severity of the COVID-19 infection and act quickly against the coronavirus SARS-CoV-2 using a large variety of tools. In this review, a panoply of nanoscience and nanotechnology approaches show how these disciplines can help the medical, technical, and scientific communities to fight the pandemic, highlighting the development of nanomaterials for detection, sanitation, therapies, and vaccines. SARS-CoV-2, which can be regarded as a functional core-shell nanoparticle (NP), can interact with diverse materials in its vicinity and remains attached for variable times while preserving its bioactivity. These studies are critical for the appropriate use of controlled disinfection systems. Other nanotechnological approaches are also decisive for the development of improved novel testing and diagnosis kits of coronavirus that are urgently required. Therapeutics are based on nanotechnology strategies as well and focus on antiviral drug design and on new nanoarchitectured vaccines. A brief overview on patented work is presented that emphasizes nanotechnology applied to coronaviruses. Finally, some comments are made on patents of the initial technological responses to COVID-19 that have already been put in practice.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanotecnologia/métodos , Pandemias , Pneumonia Viral , Antivirais/administração & dosagem , Betacoronavirus/química , Betacoronavirus/ultraestrutura , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Desinfecção/métodos , Humanos , Nanopartículas/química , Nanopartículas/ultraestrutura , Nanoestruturas/química , Nanotecnologia/legislação & jurisprudência , Pandemias/prevenção & controle , Patentes como Assunto , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Propriedades de Superfície , Vacinas Virais/administração & dosagem
5.
Anal Chem ; 92(19): 13396-13404, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: covidwho-738932

RESUMO

Rapid, accurate, reliable, and risk-free tracking of pathogenic microorganisms at the single-cell level is critical to achieve efficient source control and prevent outbreaks of microbial infectious diseases. For the first time, we report a promising approach for integrating the concepts of a remarkably large Stokes shift and dual-recognition into a single matrix to develop a pathogenic microorganism stimuli-responsive ratiometric fluorescent nanoprobe with speed, cost efficiency, stability, ultrahigh specificity, and sensitivity. As a proof-of-concept, we selected the Gram-positive bacterium Staphylococcus aureus (S. aureus) as the target analyte model, which easily bound to its recognition aptamer and the broad-spectrum glycopeptide antibiotic vancomycin (Van). To improve the specificity and short sample-to-answer time, we employed classic noncovalent π-π stacking interactions as a driving force to trigger the binding of Van and aptamer dual-functionalized near-infrared (NIR) fluorescent Apt-Van-QDs to the surface of an unreported blue fluorescent π-rich electronic carbon nanoparticles (CNPs), achieving S. aureus stimuli-responsive ratiometric nanoprobe Apt-Van-QDs@CNPs. In the assembly of Apt-Van-QDs@CNPs, the blue CNPs (energy donor) and NIR Apt-Van-QDs (energy acceptor) became close to allow the fluorescence resonance energy transfer (FRET) process, leading to a remarkable blue fluorescence quenching for the CNPs at ∼465 nm and a clear NIR fluorescence enhancement for Apt-Van-QDs at ∼725 nm. In the presence of S. aureus, the FRET process from CNPs to Apt-Van-QDs was disrupted, causing the nanoprobe Apt-Van-QDs@CNPs to display a ratiometric fluorescent response to S. aureus, which exhibited a large Stokes shift of ∼260 nm and rapid sample-to-answer detection time (∼30.0 min). As expected, the nanoprobe Apt-Van-QDs@CNPs showed an ultrahigh specificity for ratiometric fluorescence detection of S. aureus with a good detection limit of 1.0 CFU/mL, allowing the assay at single-cell level. Moreover, we also carried out the precise analysis of S. aureus in actual samples with acceptable results. We believe that this work offers new insight into the rational design of efficient ratiometric nanoprobes for rapid on-site accurate screening of pathogenic microorganisms at the single-cell level in the early stages, especially during the worldwide spread of COVID-19 today.


Assuntos
Bactérias/química , Infecções Bacterianas/diagnóstico , Infecções Bacterianas/microbiologia , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/síntese química , Nanotecnologia/métodos , Antibacterianos/farmacologia , Aptâmeros de Nucleotídeos , Infecções por Coronavirus/complicações , Infecções por Coronavirus/microbiologia , Fluorescência , Transferência Ressonante de Energia de Fluorescência , Microbiologia de Alimentos/métodos , Humanos , Nanopartículas , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/microbiologia , Sensibilidade e Especificidade , Espectroscopia de Luz Próxima ao Infravermelho , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/química , Vancomicina/farmacologia
6.
J Nanobiotechnology ; 18(1): 125, 2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: covidwho-745681

RESUMO

Incidents of viral outbreaks have increased at an alarming rate over the past decades. The most recent human coronavirus known as COVID-19 (SARS-CoV-2) has already spread around the world and shown R0 values from 2.2 to 2.68. However, the ratio between mortality and number of infections seems to be lower in this case in comparison to other human coronaviruses (such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)). These outbreaks have tested the limits of healthcare systems and have posed serious questions about management using conventional therapies and diagnostic tools. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. In this review, we discuss the use of nanotechnology for COVID-19 virus management by the development of nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and nanocarrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanotecnologia/métodos , Pandemias , Pneumonia Viral , Antivirais/administração & dosagem , Betacoronavirus/isolamento & purificação , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Desinfecção/métodos , Portadores de Fármacos , Sistemas de Liberação de Medicamentos , Humanos , Nanoestruturas/administração & dosagem , Equipamento de Proteção Individual , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Vacinas Virais/administração & dosagem
7.
Adv Healthc Mater ; 9(19): e2000979, 2020 10.
Artigo em Inglês | MEDLINE | ID: covidwho-743611

RESUMO

Researchers, engineers, and medical doctors are made aware of the severity of the COVID-19 infection and act quickly against the coronavirus SARS-CoV-2 using a large variety of tools. In this review, a panoply of nanoscience and nanotechnology approaches show how these disciplines can help the medical, technical, and scientific communities to fight the pandemic, highlighting the development of nanomaterials for detection, sanitation, therapies, and vaccines. SARS-CoV-2, which can be regarded as a functional core-shell nanoparticle (NP), can interact with diverse materials in its vicinity and remains attached for variable times while preserving its bioactivity. These studies are critical for the appropriate use of controlled disinfection systems. Other nanotechnological approaches are also decisive for the development of improved novel testing and diagnosis kits of coronavirus that are urgently required. Therapeutics are based on nanotechnology strategies as well and focus on antiviral drug design and on new nanoarchitectured vaccines. A brief overview on patented work is presented that emphasizes nanotechnology applied to coronaviruses. Finally, some comments are made on patents of the initial technological responses to COVID-19 that have already been put in practice.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Nanotecnologia/métodos , Pandemias , Pneumonia Viral , Antivirais/administração & dosagem , Betacoronavirus/química , Betacoronavirus/ultraestrutura , Técnicas de Laboratório Clínico/métodos , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Desinfecção/métodos , Humanos , Nanopartículas/química , Nanopartículas/ultraestrutura , Nanoestruturas/química , Nanotecnologia/legislação & jurisprudência , Pandemias/prevenção & controle , Patentes como Assunto , Pneumonia Viral/diagnóstico , Pneumonia Viral/prevenção & controle , Pneumonia Viral/terapia , Propriedades de Superfície , Vacinas Virais/administração & dosagem
8.
Nat Commun ; 11(1): 4117, 2020 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-32807785

RESUMO

Strategies for eradicating cancer stem cells (CSCs) are urgently required because CSCs are resistant to anticancer drugs and cause treatment failure, relapse and metastasis. Here, we show that photoactive functional nanocarbon complexes exhibit unique characteristics, such as homogeneous particle morphology, high water dispersibility, powerful photothermal conversion, rapid photoresponsivity and excellent photothermal stability. In addition, the present biologically permeable second near-infrared (NIR-II) light-induced nanocomplexes photo-thermally trigger calcium influx into target cells overexpressing the transient receptor potential vanilloid family type 2 (TRPV2). This combination of nanomaterial design and genetic engineering effectively eliminates cancer cells and suppresses stemness of cancer cells in vitro and in vivo. Finally, in molecular analyses of mechanisms, we show that inhibition of cancer stemness involves calcium-mediated dysregulation of the Wnt/ß-catenin signalling pathway. The present technological concept may lead to innovative therapies to address the global issue of refractory cancers.


Assuntos
Raios Infravermelhos , Nanotecnologia/métodos , Células-Tronco Neoplásicas/efeitos da radiação , Animais , Apoptose/efeitos da radiação , Western Blotting , Cálcio/metabolismo , Canais de Cálcio/metabolismo , Linhagem Celular Tumoral , Feminino , Citometria de Fluxo , Humanos , Imuno-Histoquímica , Células MCF-7 , Camundongos , Camundongos Endogâmicos BALB C , Microscopia de Fluorescência , Células-Tronco Neoplásicas/citologia , Células-Tronco Neoplásicas/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Canais de Cátion TRPV/metabolismo , Via de Sinalização Wnt
9.
Nat Commun ; 11(1): 4271, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32848153

RESUMO

Performing multi-color nanoscopy for extended times is challenging due to the rapid photobleaching rate of most fluorophores. Here we describe a new fluorophore (Yale-595) and a bio-orthogonal labeling strategy that enables two-color super-resolution (STED) and 3D confocal imaging of two organelles simultaneously for extended times using high-density environmentally sensitive (HIDE) probes. Because HIDE probes are small, cell-permeant molecules, they can visualize dual organelle dynamics in hard-to-transfect cell lines by super-resolution for over an order of magnitude longer than with tagged proteins. The extended time domain possible using these tools reveals dynamic nanoscale targeting between different organelles.


Assuntos
Corantes Fluorescentes , Microscopia de Fluorescência/métodos , Nanotecnologia/métodos , Organelas/metabolismo , Linhagem Celular , Corantes Fluorescentes/química , Células HeLa , Células Endoteliais da Veia Umbilical Humana , Humanos , Imageamento Tridimensional , Microscopia Confocal , Fotodegradação , Imagem com Lapso de Tempo
10.
Int J Nanomedicine ; 15: 4991-5004, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764931

RESUMO

Introduction: Various materials and approaches have been used to reduce the mesh-induced inflammatory response and modify the mesh with tissue-matched mechanical properties, aiming to improve the repair of abdominal wall defects. Materials and Methods: In this study, we fabricated a polycaprolactone (PCL)/silk fibroin (SF) mesh integrated with amoxicillin (AMX)-incorporating multiwalled carbon nanotubes (MWCNTs) via electrospinning, grafting and crosslinking, developing a sustainable antibiotic and flexible mesh. AMX was loaded into the hollow tubular MWCNTs by physical adsorption, and a nanofibrous structure was constructed by electrospinning PCL and SF (40:60 w/w). The AMX@MWCNTs were then chemically grafted onto the surfaces of the PCL/SF nanofibers by treating with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) solution for simultaneous crosslinking and coating. The incorporation of AMX into the MWCNTs (AMX@MWCNTs) and the integration of the AMX@MWCNTs with the PCL/SF nanofibers were characterized. Then, the functional mesh was fabricated and fully evaluated in terms of antibacterial activity, mechanical properties and host response. Results: Our results demonstrated that the PCL/SF nanofibrous structure was fabricated successfully by electrospinning. After integrating with AMX@MWCNT by grafting and crosslinking, the functional mesh showed undeformed structure, modified surface hydrophilicity and biocompatible interfaces, abdominal wall-matched mechanical properties, and a sustained-release antibiotic profile in E. coli growth inhibition compared to those of PCL/SF mesh in vitro. In a rat model with subcutaneous implantation, the functional mesh incited less mesh-induced inflammatory and foreign body responses than PCL/SF mesh within 14 days. The histological analysis revealed less infiltration of granulocytes and macrophages during this period, resulting in the loosely packed collagen deposition on the functional mesh and prominent collagen incorporation. Discussion: Therefore, this designed PCL/SF-AMX@MWCNT nanofibrous mesh, functionalized with antibacterial and tissue-matched mechanical properties, provides a promising alternative for the repair of abdominal wall defects.


Assuntos
Amoxicilina/química , Antibacterianos/química , Nanofibras/química , Nanotecnologia/métodos , Telas Cirúrgicas , Amoxicilina/farmacocinética , Amoxicilina/farmacologia , Animais , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Colágeno/química , Colágeno/metabolismo , Reagentes para Ligações Cruzadas/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Fibroínas/química , Inflamação/etiologia , Masculino , Teste de Materiais , Camundongos , Nanotubos de Carbono/química , Poliésteres/química , Ratos Sprague-Dawley , Telas Cirúrgicas/efeitos adversos
11.
Crit Rev Ther Drug Carrier Syst ; 37(3): 271-303, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749140

RESUMO

Nanotechnology has made great contributions in the development of materials with potential application in different areas, especially in the pharmaceutical sector, where nano-systems are being intensely studied for controlled drug release. These innovative systems are composed of structures such as nanoparticles, nanoemulsions, and cyclodextrins, with the aim of promoting enhanced bioavailability of bioactive molecules. Among these nanocarriers, vesicles such as liposomes and polymersomes are considered to be promising alternatives in delivering hydrophilic and lipophilic drugs. They have different classifications according to their composition, among which are hybrid vesicles, which unlike liposomes are composed of both lipids and polymers. These vesicular systems stand out for combining the advantages of both components, overcoming the limitations of traditional systems imposed by low stability and premature release of the encapsulated active substance. The polymers applied in hybrid vesicles can make up the membrane structure itself or be employed to coat preformed vesicles. Due to the relevance of these systems, this work covers their characteristics and summarizes recent articles about them in the literature.


Assuntos
Cosméticos/administração & dosagem , Lipídeos/administração & dosagem , Nanopartículas/administração & dosagem , Nanotecnologia/métodos , Polímeros/administração & dosagem , Nanomedicina Teranóstica/métodos , Animais , Cosméticos/química , Preparações de Ação Retardada , Sistemas de Liberação de Medicamentos/métodos , Humanos , Lipídeos/química , Lipossomos/administração & dosagem , Lipossomos/química , Nanopartículas/química , Polímeros/química
12.
Int J Mol Sci ; 21(14)2020 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-32698479

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the COVID-19 pandemic that has been spreading around the world since December 2019. More than 10 million affected cases and more than half a million deaths have been reported so far, while no vaccine is yet available as a treatment. Considering the global healthcare urgency, several techniques, including whole genome sequencing and computed tomography imaging have been employed for diagnosing infected people. Considerable efforts are also directed at detecting and preventing different modes of community transmission. Among them is the rapid detection of virus presence on different surfaces with which people may come in contact. Detection based on non-contact optical techniques is very helpful in managing the spread of the virus, and to aid in the disinfection of surfaces. Nanomaterial-based methods are proven suitable for rapid detection. Given the immense need for science led innovative solutions, this manuscript critically reviews recent literature to specifically illustrate nano-engineered effective and rapid solutions. In addition, all the different techniques are critically analyzed, compared, and contrasted to identify the most promising methods. Moreover, promising research ideas for high accuracy of detection in trace concentrations, via color change and light-sensitive nanostructures, to assist fingerprint techniques (to identify the virus at the contact surface of the gas and solid phase) are also presented.


Assuntos
Betacoronavirus/genética , Infecções por Coronavirus/diagnóstico , Estruturas Metalorgânicas/química , Nanotecnologia/métodos , Pneumonia Viral/diagnóstico , Sistemas Automatizados de Assistência Junto ao Leito , Genoma Viral/genética , Humanos , Nanopartículas Metálicas/química , Pandemias , RNA Viral/genética , Sequenciamento Completo do Genoma
13.
Nat Commun ; 11(1): 3699, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32709877

RESUMO

Mitochondria play a critical role in generating energy to support the entire lifecycle of biological cells, yet it is still unclear how their morphological structures evolve to regulate their functionality. Conventional fluorescence microscopy can only provide ~300 nm resolution, which is insufficient to visualize mitochondrial cristae. Here, we developed an enhanced squaraine variant dye (MitoESq-635) to study the dynamic structures of mitochondrial cristae in live cells with a superresolution technique. The low saturation intensity and high photostability of MitoESq-635 make it ideal for long-term, high-resolution (stimulated emission depletion) STED nanoscopy. We performed time-lapse imaging of the mitochondrial inner membrane over 50 min (3.9 s per frame, with 71.5 s dark recovery) in living HeLa cells with a resolution of 35.2 nm. The forms of the cristae during mitochondrial fusion and fission can be clearly observed. Our study demonstrates the emerging capability of optical STED nanoscopy to investigate intracellular physiological processes with nanoscale resolution for an extended period of time.


Assuntos
Ciclobutanos , Membranas Mitocondriais/ultraestrutura , Nanotecnologia/métodos , Fenóis , Linhagem Celular , Corantes Fluorescentes/química , Células HeLa , Humanos , Microscopia de Fluorescência/métodos , Mitocôndrias , Dinâmica Mitocondrial/fisiologia , Coloração e Rotulagem/métodos
14.
J Control Release ; 326: 164-171, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-32681950

RESUMO

The situation of the COVID-19 pandemic reminds us that we permanently need high-value flexible solutions to urgent clinical needs including simplified diagnostic technologies suitable for use in the field and for delivering targeted therapeutics. From our perspective nanotechnology is revealed as a vital resource for this, as a generic platform of technical solutions to tackle complex medical challenges. It is towards this perspective and focusing on nanomedicine that we take issue with Prof Park's recent editorial published in the Journal of Controlled Release. Prof. Park argued that in the last 15 years nanomedicine failed to deliver the promised innovative clinical solutions to the patients (Park, K. The beginning of the end of the nanomedicine hype. Journal of Controlled Release, 2019; 305, 221-222 [1]. We, the ETPN (European Technology Platform on Nanomedicine) [2], respectfully disagree. In fact, the more than 50 formulations currently in the market, and the recent approval of 3 key nanomedicine products (e. g. Onpattro, Hensify and Vyxeos), have demonstrated that the nanomedicine field is concretely able to design products that overcome critical barriers in conventional medicine in a unique manner, but also to deliver within the cells new drug-free therapeutic effects by using pure physical modes of action, and therefore make a difference in patients lives. Furthermore, the >400 nanomedicine formulations currently in clinical trials are expecting to bring novel clinical solutions (e.g. platforms for nucleic acid delivery), alone or in combination with other key enabling technologies to the market, including biotechnologies, microfluidics, advanced materials, biomaterials, smart systems, photonics, robotics, textiles, Big Data and ICT (information & communication technologies) more generally. However, we agree with Prof. Park that " it is time to examine the sources of difficulty in clinical translation of nanomedicine and move forward ". But for reaching this goal, the investments to support clinical translation of promising nanomedicine formulations should increase, not decrease. As recently encouraged by EMA in its roadmap to 2025, we should create more unity through a common knowledge hub linking academia, industry, healthcare providers and hopefully policy makers to reduce the current fragmentation of the standardization and regulatory body landscape. We should also promote a strategy of cross-technology innovation, support nanomedicine development as a high value and low-cost solution to answer unmet medical needs and help the most promising innovative projects of the field to get better and faster to the clinic. This global vision is the one that the ETPN chose to encourage for the last fifteen years. All actions should be taken with a clear clinical view in mind, " without any fanfare", to focus "on what matters in real life", which is the patient and his/her quality of life. This ETPN overview of achievements in nanomedicine serves to reinforce our drive towards further expanding and growing the maturity of nanomedicine for global healthcare, accelerating the pace of transformation of its great potential into tangible medical breakthroughs.


Assuntos
Sistemas de Liberação de Medicamentos , Nanomedicina , Animais , Ensaios Clínicos como Assunto , Infecções por Coronavirus/terapia , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanomedicina/métodos , Nanotecnologia/métodos , Neoplasias/terapia , Pandemias , Pneumonia Viral/terapia
15.
Nanomedicine (Lond) ; 15(21): 2085-2102, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32723142

RESUMO

The COVID-19 pandemic caused by the newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) puts the world in an unprecedented crisis, leaving behind huge human losses and deep socioeconomic damages. Due to the lack of specific treatment against SARS-CoV-2, effective vaccines and antiviral agents are urgently needed to properly restrain the COVID-19 pandemic. Repositioned drugs such as remdesivir have revealed a promising clinical efficacy against COVID-19. Interestingly, nanomedicine as a promising therapeutic approach could effectively help win the battle between coronaviruses (CoVs) and host cells. This review discusses the potential therapeutic approaches, in addition to the contribution of nanomedicine against CoVs in the fields of vaccination, diagnosis and therapy.


Assuntos
Betacoronavirus , Técnicas de Laboratório Clínico , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Nanomedicina/métodos , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/uso terapêutico , Alanina/análogos & derivados , Alanina/uso terapêutico , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Reposicionamento de Medicamentos , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Humanos , Nanotecnologia/métodos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Vacinas Sintéticas/farmacologia , Vacinas Virais/farmacologia
16.
Nat Commun ; 11(1): 3781, 2020 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-32728047

RESUMO

Nanomechanical mass spectrometry has proven to be well suited for the analysis of high mass species such as viruses. Still, the use of one-dimensional devices such as vibrating beams forces a trade-off between analysis time and mass resolution. Complex readout schemes are also required to simultaneously monitor multiple resonance modes, which degrades resolution. These issues restrict nanomechanical MS to specific species. We demonstrate here single-particle mass spectrometry with nano-optomechanical resonators fabricated with a Very Large Scale Integration process. The unique motion sensitivity of optomechanics allows designs that are impervious to particle position, stiffness or shape, opening the way to the analysis of large aspect ratio biological objects of great significance such as viruses with a tail or fibrils. Compared to top-down beam resonators with electrical read-out and state-of-the-art mass resolution, we show a three-fold improvement in capture area with no resolution degradation, despite the use of a single resonance mode.


Assuntos
Espectrometria de Massas/métodos , Nanotecnologia/métodos , Dispositivos Ópticos , Imagem Individual de Molécula/métodos , Amiloide/química , Desenho de Equipamento , Espectrometria de Massas/instrumentação , Nanopartículas/química , Nanotecnologia/instrumentação , Imagem Individual de Molécula/instrumentação , Vírus/química
17.
Life Sci ; 257: 118059, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32659368

RESUMO

Cancer includes a group of diseases involving unregulated cell growth with the potential to invade or expand to other parts of the body, resulting in an estimate of 9.6 million deaths worldwide in 2018. Manifold studies have been conducted to design more efficacious techniques for cancer therapy due to the inadequacy of conventional treatments including chemotherapy, surgery, and radiation therapy. With the advances in the biomedical applications of nanotechnology-based systems, nanomaterials have gained increasing attention as promising vehicles for targeted cancer therapy and optimizing treatment outcomes. Owing to their outstanding thermal, electrical, optical and chemical properties, carbon nanotubes (CNTs) have been profoundly studied to explore the various perspectives of their application in cancer treatment. The current study aims to review the role of CNTs whether as a carrier or mediator in cancer treatment for enhancing the efficacy as well as the specificity of therapy and reducing adverse side effects. This comprehensive review indicates that CNTs have the capability to be the next generation nanomaterials to actualize noninvasive targeted eradication of tumors. However, further studies are needed to evaluate the consequences of their biomedical application before the transition into clinical trials, since possible adverse effects of CNTs on biological systems have not been clearly understood.


Assuntos
Sistemas de Liberação de Medicamentos , Nanotubos de Carbono , Neoplasias/tratamento farmacológico , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Humanos , Nanotecnologia/métodos
18.
J Vis Exp ; (160)2020 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-32658204

RESUMO

Current strategies in DNA and RNA nanotechnology enable the self-assembly of a variety of nucleic acid nanostructures in aqueous or substantially hydrated media. In this article, we describe detailed protocols that enable the construction of nanofiber architectures in organic solvent mixtures through the self-assembly of uniquely addressable, single-stranded, gamma-modified peptide nucleic acid (γPNA) tiles. Each single-stranded tile (SST) is a 12-base γPNA oligomer composed of two concatenated modular domains of 6 bases each. Each domain can bind to a mutually complimentary domain present on neighboring strands using programmed complementarity to form nanofibers that can grow to microns in length. The SST motif is made of 9 total oligomers to enable the formation of 3-helix nanofibers. In contrast with analogous DNA nanostructures, which form diameter-monodisperse structures, these γPNA systems form nanofibers that bundle along their widths during self-assembly in organic solvent mixtures. Self-assembly protocols described here therefore also include a conventional surfactant, Sodium Dodecyl Sulfate (SDS), to reduce bundling effects.


Assuntos
Nanoestruturas/química , Nanotecnologia/métodos , Ácidos Nucleicos Peptídicos/metabolismo , Conformação de Ácido Nucleico
19.
Food Chem ; 332: 127431, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32645668

RESUMO

Illegal usage of ß-agonists as the animal growth promoters can lead to multiple harmful impacts to public health, thus detection of ß-agonists at trace level in complex sample matrixes is of great importance. In recent years, emergence of advanced nanomaterials greatly facilitates the advancement of sensors in terms of sensitivity, specificity and robustness. Plenty of nanoparticles-based sensors have been developed for ß-agonists determination. In this review, we comprehensively summarized the construction of emerging nanoparticles-based sensors (including colorimetric sensors, fluorescent sensors, chemiluminescent sensors, electrochemical sensors, electrochemiluminescent sensors, surface enhanced Raman scattering sensors, surface plasmon resonance sensors, quartz crystal microbalance sensors, etc.), and nanomaterial-based enzyme-linked immunosorbent assay (nano-ELISA). Impressively, the applications of nanoparticles-based sensors and nano-ELISAs in the detection of ß-agonists have also been summarized and discussed. In the end, future opportunities and challenges in the design construction of nanoparticles (NPs)-based sensors and their applications in ß-agonist assay are tentatively proposed.


Assuntos
Agonistas Adrenérgicos/análise , Nanoestruturas/química , Animais , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Colorimetria/instrumentação , Colorimetria/métodos , Humanos , Nanotecnologia/instrumentação , Nanotecnologia/métodos , Análise Espectral Raman/instrumentação , Análise Espectral Raman/métodos , Ressonância de Plasmônio de Superfície/instrumentação , Ressonância de Plasmônio de Superfície/métodos
20.
Nat Commun ; 11(1): 3658, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694613

RESUMO

Biological systems organize multiple hierarchical structures in parallel, and create dynamic assemblies and functions by energy dissipation. In contrast, emerging artificial non-equilibrium self-assembling systems have remained relatively simplistic concerning hierarchical design, and non-equilibrium multi-component systems are uncharted territory. Here we report a modular DNA toolbox allowing to program transient non-equilibrium multicomponent systems across hierarchical length scales by introducing chemically fueled molecular recognition orchestrated by reaction networks of concurrent ATP-powered ligation and cleavage of freely programmable DNA building blocks. Going across hierarchical levels, we demonstrate transient side-chain functionalized nucleic acid polymers, and further introduce the concept of transient cooperative multivalency as a key to bridge length scales to pioneer fuel-driven encapsulation, self-assembly of colloids, and non-equilibrium transient narcissistic colloidal self-sorting on a systems level. The fully programmable and functionalizable DNA components pave the way to design chemically fueled 4D (3 space, 1 time) molecular multicomponent systems and autonomous materials.


Assuntos
Trifosfato de Adenosina/química , Bioengenharia/métodos , DNA/química , Nanotecnologia/métodos , Coloides , DNA Ligases/química , Desoxirribonucleases de Sítio Específico do Tipo II/química , Conformação de Ácido Nucleico , Polimerização , Polímeros/química
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