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1.
Biomacromolecules ; 20(12): 4407-4418, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31609589

RESUMO

Understanding the cellular uptake mechanism of materials is of fundamental importance that would be beneficial for materials design with enhanced biological functions. Herein, we report the interplay of pharmacological and genetic approaches to minimize the possible misinterpretation on cellular uptake mechanism. A library of amphiphilic polymers was used as a model system to evaluate the reliability of such methodological interplay. To probe the cellular uptake of amphiphilic polymers, we utilized an orthogonal end-group labeling strategy to conjugate one fluorescent molecule on each polymer chain. The results from the methodological interplay with these labeled polymers revealed the off-target effects of dynasore, a well-known dynamin inhibitor. Instead of dynamin, actin was found to be an essential cellular component during the cellular uptake of these amphiphilic polymers. Our study demonstrates the importance of interplaying pharmacological and genetic approaches when evaluating the endocytic mechanism of functional materials, providing insights on understanding the cellular uptake of future therapeutic materials.

2.
Nanoscale ; 11(39): 18464-18474, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31577313

RESUMO

While cells offer numerous inspiring examples in which membrane morphology and function are controlled by interactions with viruses or proteins, we still lack design principles for controlling membrane morphology in synthetic systems. With experiments and simulations, we show that spherical nanoparticles binding to lipid-bilayer membrane vesicles results in a remarkably rich set of collective morphologies that are controllable via the particle binding energy. We separately study cationic and anionic particles, where the adhesion is tuned by addition of oppositely charged lipids to the vesicles. When the binding energy is weak relative to a characteristic membrane-bending energy, vesicles adhere to one another and form a soft solid gel, a novel and useful platform for controlled release. With larger binding energy, a transition from partial to complete wrapping of the nanoparticles causes a remarkable vesicle destruction process culminating in rupture, nanoparticle-membrane tubules, and an apparent inversion of the vesicles. These findings help unify the diverse phenomena observed previously. They also open the door to a new class of vesicle-based, closed-cell gels that are more than 99% water and can encapsulate and release on demand, and show how to drive intentional membrane remodeling for shape-responsive systems.


Assuntos
Bicamadas Lipídicas/química , Nanopartículas/química , Géis/química
3.
Macromol Biosci ; 19(9): e1900105, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31386305

RESUMO

Polymeric microcapsules have begun to attract significant interest in biomedical fields. As the interactions between cells and materials are influenced by both cell type and elasticity, silk-based microcapsules are synthesized with desirable mechanical features using layer-by-layer assembly and then the uptake of these microcapsules by BeWo b30 placental cells is investigated. Cellular uptake is enhanced with increasing of elastic modulus of the silk-based microcapsules. More importantly, the distinct microvilli of these cells behaves in a diverse manner when exposed to microcapsules with different mechanical features, including grabbing (rigidity) or random touching (soft) behavior; these factors affect the final uptake. Inspired by oocyte pickup, the grabbing behavior of the microvilli may provide valuable information with which to elucidate the specific characteristics of uptake between cells and man-made particles, particularly in the reproductive system.

4.
J Colloid Interface Sci ; 551: 101-110, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31075625

RESUMO

Carbon dots (C-dots) are superior in the aspects of excellent water solubility, good biocompatibility, environmentally friendliness and non-blinking fluorescence. In this work, highly photoluminescent small-size C-dots (QY = 18.8%, quinine sulfate as standard) with narrow size distribution (1.70 ±â€¯0.21 nm) have been synthesized by using citric acid and triethylamine through hydrothermal method. The optimal excitation and emission wavelength of C-dots are 350 nm and 437 nm, respectively. And the prepared C-dots display excitation-independent behavior due to less surface defects and uniform size. Interestingly, the fluorescence of C-dots could be rapidly and selectively quenched by Hg2+ within 200 s at room temperature without further modification. Under optimal conditions, the limit of detection (LOD) was measured to be nanomolar level (2.8 nM) with a linear range of 0.05-7 µM, lower than the previous published reports. Furthermore, our results reveal that static quenching mechanism was dominated in the process in which Hg2+ coordinate with the oxygen-containing groups of C-dots to form nonfluorescent complexes. And only the addition of Hg2+ destroyed the surface defects of C-dots resulting in the fluorescent quenching. The presence of other common interfering metal ions reported in previous literature (Ag+, Cu2+, Fe3+) do not affect the surface defects, which has rarely been reported before. Besides, this sensing platform has been further successfully applied to the label free detection of Hg2+ in tap water and living cells. These conclusions demonstrate the great potential of our C-dots in selective detection of environmental and cellular Hg2+, which may achieve a lot of achievements in clinical diagnosis and other biological researches.


Assuntos
Carbono/química , Corantes Fluorescentes/química , Mercúrio/análise , Pontos Quânticos/química , Poluentes Químicos da Água/análise , Técnicas Biossensoriais/métodos , Cátions Bivalentes , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Limite de Detecção , Nitrogênio/química , Imagem Óptica/métodos , Oxigênio/química , Tamanho da Partícula , Sensibilidade e Especificidade , Espectrometria de Fluorescência , Propriedades de Superfície
5.
Biomacromolecules ; 20(1): 435-442, 2019 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-30525500

RESUMO

RNA interference (RNAi) requires the intracellular delivery of RNA molecules to initiate the neutralization of targeted mRNA molecules, inhibiting the expression or translation of the targeted gene. Current polymers and lipids that are used to deliver RNA molecules are generally required to be positively charged, to achieve complexation with RNA and the cellular internalization. However, positive surface charge has been implicated as the reason for toxicity in many of these systems. Herein, we report a novel strategy to generate noncationic RNA-polymer complexes for RNA delivery with low cytotoxicity. We use an in situ electrostatic complexation using a methylated pyridinium group, which is simultaneously removed during the RNA binding step. The resultant complexes demonstrate successful knockdown in preimplantation mammalian embryos, thus providing a new approach for nucleic acid delivery.


Assuntos
Técnicas de Transferência de Genes , Nanoconjugados/química , Polieletrólitos/química , RNA/química , Animais , Reagentes para Ligações Cruzadas/química , Feminino , Células HeLa , Humanos , Camundongos , Nanoconjugados/efeitos adversos , Eletricidade Estática
6.
Conf Proc IEEE Eng Med Biol Soc ; 2018: 5771-5774, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30441647

RESUMO

Driver fatigue is a cause of serious accidents for heavy machinery operators. Monitoring operator position, as indicated by their Center of Gravity (CoG), may be a means to non-invasively detect driver fatigue. We prototyped a research tool that tracks CoG from four sensors located within the legs of a seat, and validated its accuracy and precision. Our primary contributions are the development of a low-cost integrated CoG detector for seated drivers and the design of a flexure structure to protect load cells from shocks, tensile and shear forces. This system will enable research into CoG as an indicator of fatigue.


Assuntos
Prevenção de Acidentes/instrumentação , Acidentes de Trabalho/prevenção & controle , Fadiga , Gravitação , Monitorização Fisiológica , Humanos
7.
Int J Nanomedicine ; 13: 4073-4082, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30034233

RESUMO

Introduction: Nanomedicine has shown a great potential in perinatal medicine because of its characteristics of sustained, controlled release and targeting ability; on the other hand, it may also lead to unexpected toxicities such as embryotoxicity and even malformation after crossing the placental barrier, but data concerning transplacental transport are scarce. Pullulan acetate (PA) nanoparticles (NPs) are a promising nanocarrier derived from natural polysaccharide; however, their transplacental transport ability and mechanism are unknown. Materials and methods: In this study, fluorescein isothiocyanate (FITC) conjugated PA (PA-FITC) was synthesized. PA-FITC NPs were characterized by dynamic light scattering, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The cytotoxicity of PA-FITC NPs at concentrations of 15, 30, 60, 125, 250, 500, 1,000 and 2,000 µg/mL was studied by cell counting kit-8. The human chorionic gonadotrophin (HCG) cytokine assay was conducted to evaluate the biological function of BeWo b30 cells. Endocytic mechanisms of PA-FITC NPs were investigated via fluorescence analysis. The monolayer properties were characterized by TEM, tight junction staining, transepithelial electrical resistance and fluorescein sodium transportation. The transport ability was measured in the cell based transwell model by confocal imaging and SEM. Results: PA-FITC NPs were almost spherical shape with a size range of 200-300 nm. Cell viability of BeWo b30 cells was up to 100% in all groups. The concentrations of HCG increased with increasing numbers of cells and culture time, which showed the good biological function of BeWo b30 cells. PA-FITC NPs were rapidly endocytosed through caveolae-mediated endocytosis and pinocytosis, with uptake inhibition rates with nystatin (NY) and colchicines (Col) of 55% and 51% respectively. BeWo b30 cell monolayer was formed over 5 days. PA-FITC NPs were found in the cytoplasm of cells on the transwell membranes; while some NPs were found in the basolateral (fetal) compartment over 24 h. Conclusion: In summary, PA-FITC NPs are nontoxic, can cross the blood-placental barrier, and show mainly internalization to BeWo b30 cells through caveolae-mediated endocytosis and pinocytosis pathways, major via the former pathway. The results could benefit the adjustment and control of the transplacental transport of nanomedicines.


Assuntos
Endocitose , Glucanos/metabolismo , Modelos Biológicos , Nanopartículas/metabolismo , Placenta/metabolismo , Transporte Biológico , Morte Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Gonadotropina Coriônica , Feminino , Feto , Fluoresceína/metabolismo , Fluoresceína-5-Isotiocianato/síntese química , Humanos , Microscopia Eletrônica de Varredura , Microscopia Eletrônica de Transmissão , Nanopartículas/ultraestrutura , Gravidez
8.
Nanoscale ; 10(16): 7382-7386, 2018 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-29652051

RESUMO

Zwitterions are promising ligands for the fabrication of non-toxic and non-interacting biomaterials. Sulfonamide-based monothiol zwitterionic ligands on gold nanocluster (AuNC) surfaces provide nanomaterials with stable colloidal properties and intense red emission in biological environments. The fluorescence intensity of the nanocluster can be modulated by reactive oxygen species (e.g. ˙OH), allowing for quantitative and selective sensing of antioxidants (e.g. ascorbic acid) in real time.

9.
Chemistry ; 24(8): 1789-1794, 2018 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-29314349

RESUMO

Specific response to the concurrent presence of two different inputs is one of the hallmarks of incorporating specificities in nature. Artificial nanoassemblies that concurrently respond to two very different inputs are of great interest in a variety of applications, especially in biomedicine. Here, we present a design strategy for amphiphilic nanoassemblies with such capabilities, enabled by photocaging a ligand moiety that is capable of binding to a specific protein. New molecular designs that offer nanoassemblies that respond to either of two inputs or only to the concurrent presence of two inputs are outlined. Such biomimetic nanoassemblies could find use in many applications, including drug delivery and diagnostics.

10.
Chem Commun (Camb) ; 53(62): 8794-8797, 2017 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-28736785

RESUMO

Endocrine disrupting chemicals (EDCs) interact with estrogen receptors (ERs), causing a broad range of adverse health effects. Current assays for EDC activity are slow and often lack sensitivity. We report here an ultra-sensitive nanosensor that can detect estrogenic cellular changes in ER(+) MCF-7 cells rapidly (minutes) at several orders of magnitude lower than the generally used assays. Notably, the sensor responses at these ultra-low EDC levels correlated with an increased synthesis phase (S-phase) cell population of EDC-treated cells. The nanosensor was also able to detect binary EDC mixture effects, with synergism observed for bisphenol A (BPA) - 17ß-estradiol (E2), and antagonism for dicyclohexylphthalate (DCHP) - E2 and benzo(a)pyrene (BaP) - E2.


Assuntos
Disruptores Endócrinos/análise , Estrogênios não Esteroides/análise , Proteínas de Fluorescência Verde/química , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Antagonismo de Drogas , Sinergismo Farmacológico , Disruptores Endócrinos/farmacologia , Estradiol/análise , Estradiol/farmacologia , Estrogênios não Esteroides/farmacologia , Ouro/química , Humanos , Células MCF-7 , Fase S/efeitos dos fármacos
11.
J Am Chem Soc ; 139(25): 8547-8551, 2017 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-28598151

RESUMO

Active intracellular transport is a central mechanism in cell biology, directed by a limited set of naturally occurring signaling peptides. Here, we report the first nonpeptide moiety that recruits intracellular transport machinery for nuclear targeting. Proteins synthetically modified with a simple aromatic boronate motif are actively trafficked to the nucleus via the importin α/ß pathway. Significantly, proteins too large to passively diffuse through nuclear pores were readily imported into the nucleus through this boronate-mediated pathway. The use of this simple motif to provide active intracellular targeting provides a promising strategy for directing subcellular localization for therapeutic and fundamental applications.


Assuntos
Ácidos Borônicos/química , Núcleo Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Ácidos Borônicos/farmacologia , Células HeLa , Humanos , Modelos Biológicos , Estrutura Molecular
12.
Nanoscale ; 8(42): 18038-18041, 2016 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-27738697

RESUMO

We report an effective intracellular delivery strategy for proteins of high molecular weight using AuNP stabilized capsules. This strategy provides direct delivery to the cytosol, avoiding endosomal entrapment.


Assuntos
Sistemas de Liberação de Medicamentos , Nanopartículas Metálicas , Nanocápsulas , Proteínas/administração & dosagem , Citosol , Endossomos , Ouro , Células HeLa , Humanos
13.
ACS Nano ; 10(9): 8732-7, 2016 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-27622756

RESUMO

Zwitterionic nanoparticles are generally considered nontoxic and noninteracting. Here, we report effective and selective antimicrobial activity of zwitterionic gold nanoparticles (AuNP) through modulation NP size and surface charge orientation. Using a set of 2, 4, and 6 nm core AuNPs, increasing particle size increased antimicrobial efficiency through bacterial membrane disruption. Further improvement was observed through control of the ligand structure, generating antimicrobial particles with low hemolytic activity and demonstrating the importance of size and surface structure in dictating the bioactivity properties of nanomaterials.


Assuntos
Anti-Infecciosos/química , Ligantes , Nanopartículas Metálicas/química , Ouro , Tamanho da Partícula
14.
Angew Chem Int Ed Engl ; 55(36): 10707-11, 2016 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-27490155

RESUMO

Rational design of organic 2D (O2D) materials has made some progress, but it is still in its infancy. A class of self-assembling small molecules is presented that form nano/microscale supramolecular 2D materials in aqueous media. A judicial combination of four different intermolecular interactions forms the basis for the robust formation of these ultrathin assemblies. These assemblies can be programmed to disassemble in response to a specific protein and release its non-covalently bound guest molecules.


Assuntos
Preparações de Ação Retardada/química , Nanoestruturas/química , Sistemas de Liberação de Medicamentos , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Nanoestruturas/ultraestrutura , Compostos Orgânicos/química , Bibliotecas de Moléculas Pequenas/química , Eletricidade Estática , Água/química
15.
ACS Nano ; 10(7): 6731-6, 2016 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-27337000

RESUMO

Differentiation between cell surface-bound and internalized nanoparticles is challenging yet essential for accurately quantifying cellular uptake. Here, we describe a versatile mass spectrometry-based method that allows separate quantification of both cell surface-bound and internalized nanoparticles. This rapid method uses tuned laser fluencies to selectively desorb and ionize cell surface-bound cationic gold nanoparticles from intact cells, providing quantification of external particles. Overall nanoparticle quantities are obtained from the cell lysates, with subtraction of external particles from the total amount providing quantification of taken-up nanoparticles. The utility of this strategy was demonstrated through simultaneous quantitative determination of how cell-surface proteoglycans influence nanoparticle binding and uptake into cells.


Assuntos
Diferenciação Celular , Ouro , Espectrometria de Massas , Nanopartículas Metálicas , Cátions , Membrana Celular , Nanopartículas
16.
Macromolecules ; 49(17): 6186-6192, 2016 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-29353939

RESUMO

A strategy to construct different stimuli responsive polymers from post polymerization modifications of a single polymer scaffold via thiol-disulfide exchange has been developed. Here, we report on a random copolymer that enables the design and syntheses of a series of dual or multi-stimuli responsive nanoassemblies using a simple post-polymerization modification step. The reactive functional group involves a side chain monopyridyl disulfide unit, which rapidly and quantitatively reacts with various thiols under mild conditions. Independent and concurrent incorporation of physical, chemical or biologically responsive properties have been demonstrated. We envision that this strategy may open up opportunities to simplify the synthesis of multi-functional polymers with broad implications in a variety of biological applications.

17.
Anal Chem ; 87(17): 8977-84, 2015 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-26172120

RESUMO

In this study, we demonstrate a bacteriophage (phage)-based magnetic separation scheme for the rapid detection of Escherichia coli (E. coli) in drinking water. T7 phage is a lytic phage with a broad host range specificity for E. coli. Our scheme was as follows: (1) T7 bacteriophage-conjugated magnetic beads were used to capture and separate E. coli BL21 from drinking water; (2) subsequent phage-mediated lysis was used to release endemic ß-galactosidase (ß-gal) from the bound bacterial cells; (3) the release of ß-gal was detected using chlorophenol red-ß-d-galactopyranoside (CRPG), a colorimetric substrate which changes from yellow to red in the presence of ß-gal. Using this strategy, we were able to detect E. coli at a concentration of 1 × 10(4) CFU·mL(-1) within 2.5 h. The specificity of the proposed magnetic probes toward E. coli was demonstrated against a background of competing bacteria. By incorporating a pre-enrichment step in Luria-Bertani (LB) broth supplemented with isopropyl ß-d-thiogalactopyranoside (IPTG), we were able to detect 10 CFU·mL(-1) in drinking water after 6 h of pre-enrichment. The colorimetric change can be determined either by visual observation or with a reader, allowing for a simple, rapid quantification of E. coli in resource-limited settings.


Assuntos
Bacteriófago T7/química , Água Potável/microbiologia , Escherichia coli/isolamento & purificação , Escherichia coli/virologia , Nanopartículas de Magnetita/química
18.
Analyst ; 140(15): 4991-6, 2015 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-26042607

RESUMO

Traditional plating and culturing methods used to quantify bacteria commonly require hours to days from sampling to results. We present here a simple, sensitive and rapid electrochemical method for bacterial detection in drinking water based on gold nanoparticle-enzyme complexes. The gold nanoparticles were functionalized with positively charged quaternary amine headgroups that could bind to enzymes through electrostatic interactions, resulting in inhibition of enzymatic activity. In the presence of bacteria, the nanoparticles were released from the enzymes and preferentially bound to the bacteria, resulting in an increase in enzyme activity, releasing a redox-active phenol from the substrate. We employed this strategy for the electrochemical sensing of Escherichia coli and Staphylococcus aureus, resulting in a rapid detection (<1 h) with high sensitivity (10(2) CFU mL(-1)).


Assuntos
Técnicas Biossensoriais/métodos , Água Potável/microbiologia , Escherichia coli/isolamento & purificação , Ouro/química , Nanopartículas Metálicas/química , Staphylococcus aureus/isolamento & purificação , beta-Galactosidase/química , Técnicas Biossensoriais/economia , Técnicas Eletroquímicas/economia , Técnicas Eletroquímicas/métodos , Enzimas Imobilizadas/química , Limite de Detecção , Nitrofenilgalactosídeos/química
19.
Tetrahedron Lett ; 56(23): 3653-3657, 2015 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-26074630

RESUMO

Host-guest interactions between a synthetic receptor, cucurbit[7]uril (CB[7]), and gold nanoparticles (AuNPs) have been quantified using isothermal titration calorimetry. AuNPs were functionalized with ligands containing tertiary or quaternary benzylamine derivatives, with electron donating or withdrawing groups at the para position of the benzene ring. Analysis of binding interactions reveals that functional groups at the para position have no significant effect on binding constant. However, headgroups bearing a permanent positive charge increased the binding of AuNPs to CB[7] ten-fold compared to monomethyl counterparts.

20.
Bioconjug Chem ; 26(6): 1004-7, 2015 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-26011555

RESUMO

We describe a method for quantitative monitoring of subcellular protein trafficking using nanoparticle-stabilized nanocapsules for protein delivery. This method provides rapid delivery of the protein into the cytosol, eliminating complications from protein homeostasis processes found with cellularly expressed proteins. After delivery, nuclear protein trafficking was followed by real time microscopic imaging. Quantitative analyses of the accumulation percentage and the import dynamics of the nuclear protein trafficking, demonstrate the utility of this method for studying intracellular trafficking systems.


Assuntos
Núcleo Celular/metabolismo , Citosol/metabolismo , Proteínas de Fluorescência Verde/administração & dosagem , Nanocápsulas/química , Nanopartículas/química , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/química , Corantes Fluorescentes/farmacocinética , Proteínas de Fluorescência Verde/química , Proteínas de Fluorescência Verde/farmacocinética , Células HeLa , Humanos , Modelos Moleculares , Sinais de Localização Nuclear , Imagem Óptica , Transporte Proteico , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/farmacocinética
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