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1.
Se Pu ; 39(10): 1128-1136, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34505435

RESUMO

Exosomes, which are extracellular vesicles with sizes of 30-150 nm, contain proteins, lipids, RNA, etc., which can reflect important information about parental cells. They also have unique structures and can perform characteristic biological functions. Although the release of exosomes is a normal process, tumor cells release more exosomes, and the contents can induce cancer progression. Exosomes are widely distributed in body fluids at high concentrations and are easy to obtain; hence, the collection of exosomes released by tumor cells has become one of the main directions in tumor liquid biopsy. In order to ensure the reproducibility and consistency of liquid biopsy results, it is necessary to develop methods for enriching exosomes in sufficient yield and purity from complex samples. Based on the size, hydrophobic proteins, and characteristic proteins of exosomes, various methods for exosome separation and purification have been developed, such as ultracentrifugation, polymer precipitation, and immunoaffinity methods. An aptamer (Apt) is an oligonucleotide chain with a total length of 20-100 nt, which has ligand binding properties and can be used to detect different types of drugs and biomolecules at the nanomolar level. Characteristic proteins on the surface of exosomes such as CD63, CD9, and CD81 are often used as exosomes markers. At present, a variety of aptamer sequences targeting the characteristic proteins of exosomes have been reported. Zirconium and titanium cations as well as the oxides of these metals show high affinity to the phospholipid bilayer on the exosome surface and are used in the separation and purification of exosomes. Metal organic frameworks (MOFs) can provide a wealth of metal oxide affinity sites to interact with the phospholipid bilayer membrane, and their diverse organic ligands can provide numerous modification sites to bind with aptamers. In this study, different metal/aptamer dual-functional composite magnetic nanomaterials were prepared by exploiting the surface chemistry and biological characteristics of exosomes for the enrichment and purification of exosomes. Because of the specific affinity of the aptamers toward the target membrane protein on the exosome surface and the affinity of the titanium or zirconium oxide toward the phospholipid bilayer membrane of exosomes, dual-functional magnetic nanomaterials can greatly improve the enrichment capacity and separation selectivity of exosomes. Fe3O4@Zr-MOFs was used as the substrate to fabricate the dual functional MOFs/metal oxide aptamer composite magnetic nanomaterial Fe3O4@Zr-MOFs-Apt. UiO-66-NH2 was grown in situ on the surface of Fe3O4 by a solvothermal method to form a Zr-MOFs layer, and aptamer-CD63 was covalently bonded to the amino group of the organic ligand of the MOFs. The magnetic bimetallic metal organic framework Fe3O4@Zr-Ti-MOFs, which was fabricated via a layer-by-layer assembly approach, was used as the substrate to prepare the dual functional MOFs/metal oxide aptamer composite Fe3O4@Zr-Ti-MOFs-Apt via coordination bond formation between the metal site on the Fe3O4@Zr-Ti-MOFs and the aptamers. The third dual functional MOFs/metal oxide aptamer composite magnetic nanomaterial, Fe3O4@TiO2-Apt, was prepared by using Fe3O4@TiO2 as the substrate via coordination bond formation between the metal site on Fe3O4@TiO2 and the aptamers. Considering model exosomes extracted by ultracentrifugation and urine as samples, this paper compared the enrichment performance of materials modified with the same quality of aptamers and different levels of metal oxides. The dual-functional composite magnetic nanomaterials modified with different metals/aptamers were used for the enrichment of urine exosomes. The obtained exosomes were lysed and identified by mass spectrometry, and 233, 343, and 832 exosomal proteins were identified. This result also shows that dual-functional magnetic nanomaterials can fully combine the high selectivity of the nucleic acid aptamer and the high enrichment capacity of the metal oxides. The rapid, efficient separation and purification of exosomes in biological samples has excellent application potential. The material design and purification methods also provide a new idea for the development of new exosome-enrichment materials.


Assuntos
Exossomos , Nanoestruturas , Fenômenos Magnéticos , Oligonucleotídeos , Reprodutibilidade dos Testes
2.
Mater Sci Eng C Mater Biol Appl ; 128: 112330, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34474881

RESUMO

Glioblastoma multiforme (GBM) is one of the most malignant types of central nervous system tumours. Despite advances in treatment modalities, it remains largely incurable with an extremely poor prognosis. Treatment of GBM is associated with several difficulties such as the risk of damaging healthy brain tissues during surgery, drug resistance and inadequate drug delivery across the blood brain barrier. The new nanomaterial graphene, has recently attracted great attention due to its unique physico-chemical characteristics, good biocompatibility, specific targeting and small size. Starting from simple drug delivery systems, the application of graphene-based nanomaterials has been extended to a versatile platform of multiple therapeutic modalities, including immunotherapy, gene therapy, photothermal therapy and photodynamic therapy. Graphene-based materials can also be engineered to integrate multiple functions into a single platform for combination therapy for enhanced anticancer activity and reduced side effects. This review aims to discuss the state-of-the-art applications of graphene-based materials in GBM diagnosis and therapy. In addition, future challenges and prospects regarding this promising field are discussed, which may pave the way towards improving the safety and efficacy of graphene-based therapeutics.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Grafite , Nanoestruturas , Fotoquimioterapia , Neoplasias Encefálicas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Glioblastoma/tratamento farmacológico , Grafite/uso terapêutico , Humanos
3.
Nanoscale ; 13(33): 13923-13942, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34477675

RESUMO

Owing to their peculiar oxidative effect, silver cations (Ag+) are well known for their antimicrobial properties and explored as therapeutic agents for biomedical applications. Size control with improved dispersion and stability are the key factors of Ag NPs (silver nanoparticles) to be used in biomedical applications. Silver based nano-materials are highly efficient due to their biological, chemical and physical properties in comparison with bulk silver. Atomic scale fabrication is achieved by rearranging the internal components of a material, in turn, influencing the mechanical, electrical, magnetic, thermal and chemical properties. For instance, size and shape have a strong impact on the optical, thermal and catalytic properties of Ag NPs. Such properties can be tuned by controlling the surface/volume ratio of Ag nanostructures with a small size (ideally <100 nm), in turn showing peculiar biological activity different from that of bulk silver. Silver nanomaterials such as nanoparticles, thin films and nanorods can be synthesized by various physical, chemical and biological methods whose most recent implementations will be described in this review. By controlling the structure-functionality relationship, silver based nano-materials have high potential for commercialization in biomedical applications. Antimicrobial, antifungal, antiviral, and anti-inflammatory Ag NPs can be applied in several fields such as pharmaceutics, sensors, coatings, cosmetics, wound healing, bio-labelling agents, antiviral drugs, and packaging.


Assuntos
Anti-Infecciosos , Nanopartículas Metálicas , Nanoestruturas , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Prata
4.
Nanoscale ; 13(33): 13943-13961, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34477676

RESUMO

Drug-radiotherapy is a common and effective combinational treatment for cancer. This study aimed to explore the ionizing radiation-optimized drug treatment based on nanomaterials so as to improve the synergistic efficacy of drug-radiotherapy against cancer and limit the adverse effect on healthy organs. In this review, these emerging strategies were divided into four parts. First, the delivery of the drug-loaded nanoparticles was optimized owing to the strengthened passive targeting process, active targeting process, and cell targeting process of nanoparticles after ionizing radiation exposure. Second, nanomaterials were designed to respond to the ionizing radiation, thus leading to the release of the loading drugs controllably. Third, radiation-activated pro-drugs were loaded onto nanoparticles for radiation-triggered drug therapy. In particular, nontoxic nanoparticles with radiosensitization capability and innocuous radio-dynamic contrast agents can be considered as radiation-activated drugs, which were discussed in this review. Fourth, according to the various synergetic mechanisms, radiotherapy could improve the drug response of cancer, obtaining optimized drug-radiotherapy. Finally, relative suggestions were provided to further optimize these aforementioned strategies. Therefore, a novel topic was selected and the emerging strategies in this region were discussed, aiming to stimulate the inspiration for the development of ionizing radiation-optimized drug treatment based on nanomaterials.


Assuntos
Nanopartículas , Nanoestruturas , Neoplasias , Preparações Farmacêuticas , Humanos , Neoplasias/tratamento farmacológico , Radiação Ionizante
5.
Nanoscale ; 13(34): 14354-14362, 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477718

RESUMO

Microencapsulation of therapeutic cells has widely advanced toward the development of treatments for various diseases, in particular seeking the protection of cell transplants from immune rejection. However, several challenges in cell therapy remain due to the lack of suitable methods to monitor in vivo microcapsule tracking, microcapsule stability and/or altered cell viability and proliferation upon transplantation. We propose in this work the incorporation of contrast agents in microcapsules, which can be easily visualized by SERS imaging. By placing SERS probes in the alginate extracellular layer, a high contrast can be obtained with negligible toxicity. Specifically, we used a pH-sensitive SERS tracking probe consisting of gold nanostars encoded with a pH-sensitive Raman-active molecule, and protected by a layer of biocompatible polymer coating, grafted on the nanoparticles via electrostatic interactions. This nanomaterial is highly sensitive within the biologically relevant pH range, 5.5-7.8. We demonstrate that this SERS-based pH sensor can provide information about cell death of microencapsulated cells, in a non-invasive manner. As a result, we expect that this approach should provide a general strategy to study biological interactions at the microcapsule level.


Assuntos
Ouro , Nanoestruturas , Cápsulas , Sobrevivência Celular , Concentração de Íons de Hidrogênio
6.
Nanoscale ; 13(31): 13318-13327, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34477738

RESUMO

Investigation of the self-assembly of peptides is critically important to clarify certain biophysical phenomena, fulfill some biological functions, and construct functional materials. However, it is still a challenge to precisely predict the self-assembled structures of peptides because of their complicated driving forces and various assembling pathways. In this work, to elucidate the effects of noncovalent interactions including hydrogen bonding, molecular geometry, and hydrophobic and electrostatic interactions on the peptide self-assembly, a series of asymmetric bolaamphiphilic short peptides consisting of Ac-EI3K-NH2 (EI3K), Ac-EI4K-NH2 (EI4K), Ac-KI3E-NH2 (KI3E) and Ac-KI4E-NH2 (KI4E) were designed and their self-assembling behaviors at different solution pH values were investigated systematically. The peptides self-assembled into twisted nanofibers under most conditions except for EI4K in a strongly alkaline solution and KI4E under a strongly acidic condition, in which they self-assembled into nanotubes via helical monolayer nanosheet intermediates. In particular, KI4E nanotubes are formed under acidic conditions, and its diameters are ∼500 nm much greater than most of the self-assembled structures from bolaamphiphilic peptides. Moreover, reversible morphological transition between the nanotubes and twisted nanofibers was observed with the change in solution pH. Such tunable self-assembled structures and switchable surface properties of the asymmetric bolaamphiphilic short-peptides allow them to be used as templates to construct advanced materials. Silica and titania nanomaterials faithful to the peptide templates in morphology were prepared at ambient temperature. This work clearly elucidates the effects of noncovalent interactions on the peptide self-assembly and also provides new insights into the design and preparation of complicated inorganic materials from tunable organic templates.


Assuntos
Nanoestruturas , Dióxido de Silício , Interações Hidrofóbicas e Hidrofílicas , Peptídeos , Titânio
7.
Nanoscale ; 13(31): 13401-13409, 2021 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-34477745

RESUMO

Enzymes are the most efficient catalysts in nature that possess an impressive range of catalytic activities, albeit limited by stability in adverse conditions. Functional peptides have emerged as alternative robust biocatalysts to mimic complex enzymes. Here, a rational design of minimalistic amyloid-inspired peptides 1-2 is demonstrated, which leads to pathway-driven self-assembly triggered by heat, light and chemical cues to render 1D and 2D nanostructures by the interplay of hydrogen bonding, host-guest interaction and reversible photodimerization. Such in situ transformable peptide nanostructures by means of external cues are envisaged as a catalytic amyloid for the first time to mimic the hydrolase enzyme activity. Michaelis Menten's enzyme kinetic parameters for the hydrolysis rate correlate the external cue-mediated structure-function augmentation with the twisted bundles, 1TB being the most efficient biocatalyst among all the dimensionally diverse nanostructures. Unlike the natural enzyme, the peptide nanostructures exhibited the robust nature of the hydrolase activity over a broad range of temperature and pH. Finally, the peptide nanostructures are explored as efficient heterogeneous flow catalysts to improve the turnover number for the hydrolase activity.


Assuntos
Hidrolases , Nanoestruturas , Catálise , Ligação de Hidrogênio , Peptídeos
8.
Nanoscale ; 13(30): 12848-12853, 2021 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477769

RESUMO

Nucleic acid nanostructures are promising biomaterials for the delivery of homologous gene therapy drugs. Herein, we report a facile strategy for the construction of target mRNA (scaffold) and antisense (staple strands) co-assembled RNA/DNA hybrid "origami" for efficient gene therapy. In our design, the mRNA was folded into a chemically well-defined nanostructure through RNA-DNA hybridization with high yield. After the incorporation of an active cell-targeting aptamer, the tailored RNA/DNA hybrid origami demonstrated efficient cellular uptake and controllable release of antisenses in response to intracellular RNase H digestion. The biocompatible RNA/DNA origami (RDO) elicited a noticeable inhibition of cell proliferation based on the silencing of the tumor-associated gene polo-like kinase 1 (PLK1). This RDO-based nanoplatform provides a novel strategy for the further development of gene therapy.


Assuntos
Nanoestruturas , RNA , DNA/genética , Terapia Genética , Conformação de Ácido Nucleico , Hibridização de Ácido Nucleico , RNA/genética
9.
Se Pu ; 39(9): 981-988, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34486837

RESUMO

Protein glycosylation is among the most common and important post-translational modifications, and plays an important regulatory role in many biological processes, including signal transduction, protein translation, and immune response. Abnormal protein glycosylation is also associated with numerous diseases, suggesting that glycoproteins may offer an array of useful disease biomarkers. Mass spectrometry (MS) has become an important analytical tool in glycoproteomics. However, the low abundance and weak ionization efficiency of glycopeptides have hindered direct mass spectrometric analyses, which remain considerably challenging. Glycoprotein and glycopeptide enrichment from complex biological samples is an important step in glycoproteomics. Diverse methods have recently been developed for specific glycoprotein and glycopeptide enrichment, including hydrophilic interaction liquid chromatography (HILIC), lectin affinity chromatography, boronate affinity chromatography, and hydrazide functional affinity chromatography. A variety of enrichment materials designed for the above strategies have been developed to meet the requirement of enriching low abundance glycoproteins and glycopeptides in complex samples. Magnetic solid phase extraction (MSPE) is an efficient sample pretreatment technology that offers advantages of simple operation, low cost, and high extraction efficiency. Functionalized magnetic nanomaterials have been widely used as adsorbents in glycoproteome studies. Since magnetic adsorbent is a key factor in MSPE, in this review, the preparation of magnetic nanomaterials functionalized with sugars, ionic liquids, lectins, boronate affinity ligands, metal organic frameworks, and covalent organic frameworks, and their applications in glycoprotein and glycopeptide enrichment are summarized. These functional magnetic nanomaterials possess high specific surface area and a large number of active adsorption sites, allowing different enrichment mechanisms, including HILIC, lectin affinity chromatography, and boronate and hydrazide functional affinity chromatography. These functional magnetic nanomaterials are mainly used to enrich glycoproteins and glycopeptides in serum, plasma, cells, tissues, saliva and other biological samples. Nearly 90 papers published in the last decade from the Science Citation Index (SCI) and Chinese core journals have been cited in this paper. Finally, the development and prospects of magnetic nanomaterials in glycoprotein and glycopeptide enrichment are also discussed.


Assuntos
Glicopeptídeos , Nanoestruturas , Glicoproteínas , Interações Hidrofóbicas e Hidrofílicas , Fenômenos Magnéticos , Proteoma
11.
Int J Mol Sci ; 22(15)2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34360734

RESUMO

Biomimetic design provides novel opportunities for enhancing and functionalizing biomaterials. Here we created a zirconia surface with cactus-inspired meso-scale spikes and bone-inspired nano-scale trabecular architecture and examined its biological activity in bone generation and integration. Crisscrossing laser etching successfully engraved 60 µm wide, cactus-inspired spikes on yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) with 200-300 nm trabecular bone-inspired interwoven structures on the entire surface. The height of the spikes was varied from 20 to 80 µm for optimization. Average roughness (Sa) increased from 0.10 µm (polished smooth surface) to 18.14 µm (80 µm-high spikes), while the surface area increased by up to 4.43 times. The measured dimensions of the spikes almost perfectly correlated with their estimated dimensions (R2 = 0.998). The dimensional error of forming the architecture was 1% as a coefficient of variation. Bone marrow-derived osteoblasts were cultured on a polished surface and on meso- and nano-scale hybrid textured surfaces with different spike heights. The osteoblastic differentiation was significantly promoted on the hybrid-textured surfaces compared with the polished surface, and among them the hybrid-textured surface with 40 µm-high spikes showed unparalleled performance. In vivo bone-implant integration also peaked when the hybrid-textured surface had 40 µm-high spikes. The relationships between the spike height and measures of osteoblast differentiation and the strength of bone and implant integration were non-linear. The controllable creation of meso- and nano-scale hybrid biomimetic surfaces established in this study may provide a novel technological platform and design strategy for future development of biomaterial surfaces to improve bone integration and regeneration.


Assuntos
Materiais Biomiméticos , Diferenciação Celular/efeitos dos fármacos , Nanoestruturas/química , Osteoblastos/metabolismo , Osteogênese/efeitos dos fármacos , Zircônio , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Cactaceae , Masculino , Nanoestruturas/ultraestrutura , Osteoblastos/citologia , Ratos , Ratos Sprague-Dawley , Zircônio/química , Zircônio/farmacologia
12.
Molecules ; 26(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34361740

RESUMO

There is a challenging need for the development of new alternative nanostructures that can allow the coupling and/or encapsulation of therapeutic/diagnostic molecules while reducing their toxicity and improving their circulation and in-vivo targeting. Among the new materials using natural building blocks, peptides have attracted significant interest because of their simple structure, relative chemical and physical stability, diversity of sequences and forms, their easy functionalization with (bio)molecules and the possibility of synthesizing them in large quantities. A number of them have the ability to self-assemble into nanotubes, -spheres, -vesicles or -rods under mild conditions, which opens up new applications in biology and nanomedicine due to their intrinsic biocompatibility and biodegradability as well as their surface chemical reactivity via amino- and carboxyl groups. In order to obtain nanostructures suitable for biomedical applications, the structure, size, shape and surface chemistry of these nanoplatforms must be optimized. These properties depend directly on the nature and sequence of the amino acids that constitute them. It is therefore essential to control the order in which the amino acids are introduced during the synthesis of short peptide chains and to evaluate their in-vitro and in-vivo physico-chemical properties before testing them for biomedical applications. This review therefore focuses on the synthesis, functionalization and characterization of peptide sequences that can self-assemble to form nanostructures. The synthesis in batch or with new continuous flow and microflow techniques will be described and compared in terms of amino acids sequence, purification processes, functionalization or encapsulation of targeting ligands, imaging probes as well as therapeutic molecules. Their chemical and biological characterization will be presented to evaluate their purity, toxicity, biocompatibility and biodistribution, and some therapeutic properties in vitro and in vivo. Finally, their main applications in the biomedical field will be presented so as to highlight their importance and advantages over classical nanostructures.


Assuntos
Materiais Biocompatíveis/síntese química , Portadores de Fármacos/síntese química , Nanoestruturas/química , Peptídeos/síntese química , Técnicas de Síntese em Fase Sólida/métodos , Sequência de Aminoácidos , Animais , Materiais Biocompatíveis/farmacocinética , Portadores de Fármacos/farmacocinética , Composição de Medicamentos/métodos , Humanos , Nanoestruturas/administração & dosagem , Nanoestruturas/ultraestrutura , Tamanho da Partícula , Peptídeos/farmacocinética , Distribuição Tecidual
13.
Nat Commun ; 12(1): 4994, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404799

RESUMO

We present a simple and effective scheme of a dynamic switch for DNA nanostructures. Under such a framework of toehold-free strand displacement, blocking strands at an excess amount are applied to displace the complementation of specific segments of paired duplexes. The functional mechanism of the scheme is illustrated by modelling the base pairing kinetics of competing strands on a target strand. Simulation reveals the unique properties of toehold-free strand displacement in equilibrium control, which can be leveraged for information processing. Based on the controllable dynamics in the binding of preformed DNA nanostructures, a multi-input-multi-output (MIMO) Boolean function is controlled by the presence of the blockers. In conclusion, we implement two MIMO Boolean functions (one with 4-bit input and 2-bit output, and the other with 16-bit input and 8-bit output) to showcase the controllable dynamics.


Assuntos
DNA/química , Nanoestruturas , Eletroforese , Simulação de Dinâmica Molecular , Recombinação Genética
14.
Huan Jing Ke Xue ; 42(9): 4350-4357, 2021 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-34414733

RESUMO

The release of manufactured nanomaterials (MNMs) into the environment has raised concerns about combined toxicological risks, as MNMs could significantly alter the environmental behavior and fate of co-existing contaminants. Numerous studies have been published on the combined toxicity of MNMs and co-existing contaminants, but the potential mechanisms controlling the combined toxicity, especially the biological response mechanism, remain unclear. This study investigated the combined toxicity of nano-titanium dioxide (nTiO2), a typical MNM, and the heavy metal cadmium (Cd2+), using Scenedesmus obliquus as the test organism. The molecular mechanism was examined under different concentrations, using an equivalent dose (toxic ratio 1 ∶1) on S. obliquus. The results showed that the 72h-EC50 of nTiO2 and Cd2+ at the equivalent dose was significantly higher than that of single exposure, indicating an antagonistic effect. Further transcriptomics analysis revealed that the photosynthesis, chlorophyll metabolism, and starch and sucrose metabolism pathways involved in the energy metabolism of S. obliquus were significantly up-regulated in the presence of nTiO2. The arginine and proline metabolic pathways related to the anti-stress effect of algae cells also showed positive stimulation. The results of this study provide an important reference and a research basis for in-depth understanding of the environmental effects of MNMs and co-existing contaminants.


Assuntos
Clorofíceas , Nanoestruturas , Scenedesmus , Cádmio/toxicidade
15.
J Chem Phys ; 155(5): 055102, 2021 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-34364335

RESUMO

Ratcheted multi-step hopping electron transfer systems can plausibly produce directional charge transport over very large distances without requiring a source-drain voltage bias. We examine molecular strategies to realize ratcheted charge transport based on multi-step charge hopping, and we illustrate two ratcheting mechanisms with examples based on DNA structures. The charge transport times and currents that may be generated in these assemblies are also estimated using kinetic simulations. The first ratcheting mechanism described for nanoscale systems requires local electric fields on the 109 V/m scale to realize nearly 100% population transport. The second ratcheting mechanism for even larger systems, based on electrochemical gating, is estimated to generate currents as large as 0.1 pA for DNA structures that are a few µm in length with a gate voltage of about 5 V, a magnitude comparable to currents measured in DNA wires at the nanoscale when a source-drain voltage bias of similar magnitude is applied, suggesting an approach to considerably extend the distance range over which DNA charge transport devices may operate.


Assuntos
DNA/química , Nanoestruturas/química , Condutividade Elétrica , Eletroquímica , Cinética , Eletricidade Estática
16.
Nat Commun ; 12(1): 4849, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381032

RESUMO

Although various artificial protein nanoarchitectures have been constructed, controlling the transformation between different protein assemblies has largely been unexplored. Here, we describe an approach to realize the self-assembly transformation of dimeric building blocks by adjusting their geometric arrangement. Thermotoga maritima ferritin (TmFtn) naturally occurs as a dimer; twelve of these dimers interact with each other in a head-to-side manner to generate 24-meric hollow protein nanocage in the presence of Ca2+ or PEG. By tuning two contiguous dimeric proteins to interact in a fully or partially side-by-side fashion through protein interface redesign, we can render the self-assembly transformation of such dimeric building blocks from the protein nanocage to filament, nanorod and nanoribbon in response to multiple external stimuli. We show similar dimeric protein building blocks can generate three kinds of protein materials in a manner that highly resembles natural pentamer building blocks from viral capsids that form different protein assemblies.


Assuntos
Nanoestruturas/química , Proteínas/química , Cálcio/química , Ferritinas/química , Nanoestruturas/ultraestrutura , Nanotecnologia , Polietilenoglicóis/química , Multimerização Proteica , Thermotoga maritima
17.
Anal Chem ; 93(32): 11159-11166, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34347435

RESUMO

Phenotypic plasticity is an emerging paradigm for providing biological and clinical insights into cancer initiation, progression, and resistance to therapy. However, it is a great challenge to track phenotypic information on live cells with high levels of sensitivity, specificity, and simplicity, when a specific cancer-cell subset is being targeted. In this work, we have successfully achieved cascade assembly of nanoparticles on the surface of specific cancer cells by designing a dual-aptamer-weaved molecular AND logic system. Taking advantage of spatial addressability, precise controllability, and targeting recognition of the nanostructure assemblies, we can precisely label the target-cell subset in a large population of similar cells and rapidly obtain phenotypic information in response to the surface changes of captured cancer cells. Without sophisticated instruments, we can know the phenotypic information on HepG2 cells in whole blood with a high level of sensitivity and rapid naked-eye tracking of on-cell phenotype changes of HepG2 cells undergoing epithelial-mesenchymal transition.


Assuntos
Aptâmeros de Nucleotídeos , Nanoestruturas , Tecnologia de Rastreamento Ocular , Células Hep G2 , Humanos , Fenótipo
18.
Nanomedicine (Lond) ; 16(21): 1839-1842, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34348476
19.
Environ Pollut ; 286: 117571, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34438494

RESUMO

Silver nanomaterials (AgNMs) are broadly used and among the most studied nanomaterials. The underlying molecular mechanisms (e.g. protein and metabolite response) that precede phenotypical effects have been assessed to a much lesser extent. In this paper, we assess differentially expressed proteins (DEPs) and metabolites (DEMs) by high-throughput (HTP) techniques (HPLC-MS/MS with tandem mass tags, reversed-phase (RP) and hydrophilic interaction liquid chromatography (HILIC) with mass spectrometric detection). In a time series (0, 7, 14 days), the standard soil model Enchytraeus crypticus was exposed to AgNM300K and AgNO3 at the reproduction EC20 and EC50. The impact on proteins/metabolites was clearly larger after 14 days. NM300K caused more upregulated DEPs/DEMs, more so at the EC20, whereas AgNO3 caused a dose response increase of DEPs/DEMs. Similar pathways were activated, although often via opposite regulation (up vs down) of DEPs, hence, dissimilar mechanisms underlie the apical observed impact. Affected pathways included e.g. energy and lipid metabolism and oxidative stress. Uniquely affected by AgNO3 was catalase, malate dehydrogenase and ATP-citrate synthase, and heat shock proteins (HSP70) and ferritin were affected by AgNM300K. The gene expression-based data in Adverse Outcome Pathway was confirmed and additional key events added, e.g. regulation of catalase and heat shock proteins were confirmed to be included. Finally, we observed (as we have seen before) that lower concentration of the NM caused higher biological impact. Data was deposited to ProteomeXchange, identifier PXD024444.


Assuntos
Nanopartículas Metálicas , Nanoestruturas , Poluentes do Solo , Íons , Metabolômica , Nanopartículas Metálicas/toxicidade , Nanoestruturas/toxicidade , Proteômica , Prata/toxicidade , Poluentes do Solo/análise , Espectrometria de Massas em Tandem , Transcriptoma
20.
J Biomed Nanotechnol ; 17(7): 1249-1272, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34446130

RESUMO

With the development of nanomaterials, fluorescent nanoprobes have attracted enormous attention in the fields of chemical sensing, optical materials, and biological detection. In this paper, the advantages of "off-on" fluorescent nanoprobes in disease detection, such as high sensitivity and short response time, are attentively highlighted. The characteristics, sensing mechanisms, and classifications of disease-related target substances, along with applications of these nanoprobes in cancer diagnosis and therapy are summarized systematically. In addition, the prospects of "off-on" fluorescent nanoprobe in disease detection are predicted. In this review, we presented information from all the papers published in the last 5 years discussing "off-on" fluorescent nanoprobes. This review was written in the hopes of being useful to researchers who are interested in further developing fluorescent nanoprobes. The characteristics of these nanoprobes are explained systematically, and data references and supports for biological analysis, clinical drug improvement, and disease detection have been provided appropriately.


Assuntos
Nanoestruturas , Corantes Fluorescentes
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