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1.
Artigo em Inglês | MEDLINE | ID: mdl-32486636

RESUMO

Helicobacter pylori (H. pylori) eradication by antibiotics and proton pump inhibitor treatment is limited by the low pH microenvironment in the stomach and can lead to antibiotic resistance. We fabricated fullerenol nanoparticles (FNPs) with varied chemical structures responding to a pinacol rearrangement of vicinal hydroxyl to form carbonyls in low pH environments. An obvious increase in C═O/C-O was induced in low pH and was positively correlated with a peroxidase-like activity. The FNPs exerted an excellent effect on H. pylori eradication in vitro and in vivo because of their peroxidase-like activity. FNP treatment of a H. pylori biofilm revealed that FNPs broke down polysaccharides in cell wall components, resulting in collapse of the bacteria. The cycles of FNPs combining and dissociating with the peroxidase substrate were detected by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and confirmed that FNPs enhance peroxidase-like activity. Further, the isothermal titration calorimetry results showed that FNPs with more C═O/C-O had greater affinity to bind the peroxidase substrates. Therefore, we suggest that varied C═O/C-O serves as a switch to respond to low pH in the stomach to kill H. pylori by inducing a peroxidase-like activity. FNPs can also overcome the challenge of antibiotic resistance to achieve H. pylori eradication in the stomach.

2.
Chem Commun (Camb) ; 56(54): 7427-7430, 2020 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-32490866

RESUMO

Homogeneous DNA-only keypad locks were built with multi-stranded scalable junction substrates and a series of double-stranded eliminators to differentially process correctly- and wrongly-added DNA inputs, respectively. Unlike conventional strategies that employed solid-phase platforms, one-pot assay of multiple DNA inputs was achieved, showing merits in fabricating complicated information security systems.

3.
ACS Nano ; 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32579339

RESUMO

Toehold-mediated strand displacement reaction, the fundamental basis in dynamic DNA nanotechnology, has proven its extraordinary power in programming dynamic molecular systems. Programmed activation of the toehold in a DNA substrate is crucial for building sophisticated DNA devices with digital and dynamic behaviors. Here we developed a detachable DNA circuit by embedding a pH-controlled intermolecular triplex between the toehold and branch migration domain of the traditional "linear substrate". The reaction rate and the "on/off" state of the detachable circuit can be regulated by varying the pHs. Similarly, a two-input circuit composed of three pH-responsive DNA modules was then constructed. Most importantly, a resettable self-assembly system of spherical nucleic acids was built by utilizing the high detachability of the intermolecular triplex structure-based DNA circuit. This work demonstrated a dynamic DNA device that can be repeatedly operated at constant temperature without generating additional waste DNA products. Moreover, this strategy showed an example of recycling waste spherical nucleic acids from a self-assembly system of spherical nucleic acids. Our strategy will provide a facile approach for dynamic regulation of complex molecular systems and reprogrammable nanoparticle assembly structures.

4.
Nanoscale ; 12(22): 12174-12176, 2020 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-32478778

RESUMO

Correction for 'Modulated podosome patterning in osteoclasts by fullerenol nanoparticles disturbs the bone resorption for osteoporosis treatment' by Kui Chen et al., Nanoscale, 2020, 12, 9359-9365, DOI: 10.1039/D0NR01625J.

5.
Nanoscale ; 12(17): 9359-9365, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32315013

RESUMO

Overactivation and excessive differentiation of osteoclasts (OCs) has been implicated in the course of bone metabolism-related diseases. Although fullerenol nanoparticles (fNPs) have been suggested to inhibit OC differentiation and OC function in our previous work, systemic studies on the effect of fNPs on bone diseases, e.g., osteoporosis (OP), in vivo remain elusive. Herein, it is demonstrated that fNPs significantly suppress the differentiation of OCs that derived from the murine bone marrow monocytes and inhibit the formation of the sealing zone by blocking the formation and patterning of podosomes in OCs spatiotemporally. In vivo, fNPs are supposed to be an efficient inhibitor of the overactivation of OCs in a LPS-induced bone erosion mouse model. The therapeutic effect of fNPs on osteoporosis is also investigated in an ovariectomy-induced osteoporosis rat model. The well-organized trabecular bone, the reduction in the number of TRAP positive cells, the improvement of bone-associated parameters, and the mechanical properties all demonstrate that fNPs, similar to diphosphonates, can be a promising candidate for the effective treatment of osteoporosis.

6.
Proc Natl Acad Sci U S A ; 117(11): 5617-5623, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32132205

RESUMO

As a strategy for regulating entropy, thermal annealing is a commonly adopted approach for controlling dynamic pathways in colloid assembly. By coupling DNA strand-displacement circuits with DNA-functionalized colloid assembly, we developed an enthalpy-mediated strategy for achieving the same goal while working at a constant temperature. Using this tractable approach allows colloidal bonding to be programmed for synchronization with colloid assembly, thereby realizing the optimal programmability of DNA-functionalized colloids. We applied this strategy to conditionally activate colloid assembly and dynamically switch colloid identities by reconfiguring DNA molecular architectures, thereby achieving orderly structural transformations; leveraging the advantage of room-temperature assembly, we used this method to prepare a lattice of temperature-sensitive proteins and gold nanoparticles. This approach bridges two subfields: dynamic DNA nanotechnology and DNA-functionalized colloid programming.


Assuntos
DNA/química , Nanopartículas Metálicas/química , Polímeros Responsivos a Estímulos/química , Pareamento de Bases , Coloides/química , Ouro/química , Simulação de Dinâmica Molecular , Pressão , Conformação Proteica , Temperatura , Termodinâmica
7.
ACS Nano ; 14(4): 4007-4013, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32167282

RESUMO

We have now constructed a four-legged DNA walker based on toehold exchange reactions whose movement is controlled by alternating pH changes. A well-characterized, pH-responsive CG-C+ triplex DNA was embedded into a tetrameric catalytic hairpin assembly (CHA) walker. The proton-controlled walker could autonomously move on otherwise unprogrammed microparticles surface, and the walking rate and steps of walking were efficiently controlled by pH. The starting and stopping of the walker, and its association and dissociation from the microparticles, could also be dynamically controlled by pH. The simple, programmable, and robust nature of this proton-controlled walker now provides the impetus for the development of a wide variety of more practical nanomachines.

8.
ACS Appl Mater Interfaces ; 12(13): 14958-14970, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32142246

RESUMO

We report the construction of blood cell membrane cloaked mesoporous silica nanoparticles for delivery of nanoparticles [fullerenols (Fols)] with fibrinolysis activity which endows the active Fol with successful thrombolysis effect in vivo. In vitro, Fols present excellent fibrinolysis activity, and the Fol with the best fibrinolysis activity is screened based on the correlation between Fols' structure and their fibrinolysis activity. However, the thrombolytic effect in vivo is not satisfactory. To rectify the unsatisfactory situation and avoid the exogenous stimuli, a natural blood cell membrane cloaking strategy with loading the active Fol is chosen to explore as a novel thrombolysis drug. After cloaking, the therapeutic platform prolongs blood circulation time and enhances the targeting effect. Interestingly, compared with platelet membrane cloaking, red blood cell (RBC) membrane cloaking demonstrates stronger affinity with fibrin and more enrichment at the thrombus site. The Fol with RBC cloaking shows quick and efficient thrombolysis efficacy in vivo with less bleeding risk, more excellent blood compatibility, and better biosafety when compared with the clinical drug urokinase (UK). These findings not only validate the blood cell membrane cloaking strategy as an effective platform for Fol delivery on thrombolysis treatment, but also hold a great promising solution for other active nanoparticle deliveries in vivo.

9.
Nanoscale ; 12(4): 2686-2694, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31916567

RESUMO

Carbon nanocones (CNCs) are promising drug delivery systems that can be functionalized with a variety of biomolecules (such as proteins, peptides, or antibodies), which allow for site-specific, targeted payload delivery to particular cells and organs. However, considerable uncertainty exists with respect to the toxicity of CNCs on their conical shape, and the underlying mechanism that leads to the penetration of CNCs (especially the truncated ones) in and through the cell membrane is not yet well understood. Using a coarse-grained dissipative particle dynamics method, we systematically investigate the spontaneous penetration of untruncated and truncated CNCs into membrane vesicles. For untruncated CNCs, the simulation results show that both pristine and oxidized ones can spontaneously penetrate across or be attached to the vesicle surface without membrane rupture, indicating low or insignificant toxicity. However, for truncated CNCs, we find that both the apex angle and aspect ratio can influence the CNC-membrane interactions and CNC-induced toxicity: a higher apex angle (and/or a lower aspect ratio) yields a higher toxicity of truncated CNCs. Further free energy analysis reveals that the lowest free energy path during the penetration is associated with CNC's orientation and rotation. For a truncated CNC with a low aspect ratio and high apex angle, it tends to rotate itself to a preferred standing-up fashion inside the vesicle membrane, posing an enhanced toxicity of CNCs. These findings may provide useful guidelines for designing effective CNC vehicles for drug delivery.

11.
Chem Commun (Camb) ; 55(77): 11615-11618, 2019 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-31501837

RESUMO

To date, implementation of renewable DNA circuits remains challenging due to issues including reactant depletion and waste accumulation. Herein we simultaneously addressed both issues through nicking enzyme-assisted waste-to-reactant transformation. As a proof-of-concept, a renewable entropy-driven catalytic DNA circuit was implemented, exhibiting a good renewability when replenishing fuel.


Assuntos
DNA Catalítico/química , Endonucleases/química , Redes Reguladoras de Genes , Pareamento Incorreto de Bases , Catálise , Entropia , Corantes Fluorescentes/química , Cinética , Conformação de Ácido Nucleico , Estudo de Prova de Conceito , Espectrometria de Fluorescência
12.
J Phys Chem Lett ; : 4829-4835, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31380654

RESUMO

The mechanics of DNA bending is crucially related to many vital biological processes. Recent experiments reported anomalous flexibility for DNA on short length scales, calling into doubt the validity of the harmonic worm-like chain (WLC) model in this region. In the present work, we systematically probed the bending dynamics of DNA at different length scales. In contrast to the remarkable deviation from the WLC description for DNA duplexes of less than three helical turns, our atomistic studies indicate that the neutral "null isomer" behaves in accord with the ideal elastic WLC and exhibits a uniform decay for the directional correlation of local bending. The backbone neutralization weakens the anisotropy in the effective bending preference and the helical periodicity of bend correlation that have previously been observed for normal DNA. The contribution of electrostatic repulsion to stretching cooperativity and the mechanical properties of DNA strands is length-scale-dependent: the phosphate neutralization increases the stiffness of DNA below two helical turns, but it is decreased for longer strands. We find that DNA rigidity is largely determined by base pair stacking, with electrostatic interactions contributing only around 10% of the total persistence length.

13.
J Mater Chem B ; 7(36): 5554-5562, 2019 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-31465072

RESUMO

DNA-functionalized gold nanoparticles (DNA-AuNPs) have shown great potential and exciting opportunities for constructing machine-like nanodevices. Nonthiolated DNA can be grafted onto gold surfaces via DNA bases, such as polyadenine (polyA)-DNA. The colloidal stability of polyA-DNA-AuNPs has a significant dependency on salt and pH that affects the assembly of AuNPs and their application in polyA-DNA molecular machines. High salt and low pH value contribute to the stabilization of polyA-DNA-AuNPs. In acid conditions, adenine can be protonated and becomes positively-charged, thus enhancing the adsorption of polyA-DNA onto the gold surface by electrostatic interactions; coordination of multiple interactions achieves a high DNA grafting density and colloidal stability. In addition, the length of adenine has an important effect on the efficiency of the DNA machine, while the length of thymine has little effect when the thymine length is less than or equal to seven. The assembly of AuNPs driven by dynamic polyA-DNA molecular machines was successfully accomplished with A5-DNA and A9-DNA. A moderate concentration of catalyst oligomer (50 nM) could improve the DNA hybridization efficiency. The A9-DNA based molecular machine is more efficient than the A5-DNA based one because of the larger amount of A9-DNA on the AuNPs, which increases the probability of collisions between complementary DNA strands. Therefore, polyA-DNA functionalized nanoparticles can be used as a basic unit to construct assembly-ordering structures and achieve dynamic molecular machines to be applied in the molecular diagnostics field.

14.
Langmuir ; 35(25): 8316-8324, 2019 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-31140816

RESUMO

Various polymer brushes with linear and looped conformations have gained considerable attention in the application of biomaterials and nanotechnology. In this work, the linear and looped polymer brush shells based on PEG-SH and SH-PEG-SH chains binding to gold nanoparticles (AuNPs) are synthesized. The structure and topology of the PEGylated AuNPs are systematically investigated. The basic physicochemical parameters of these PEGylated AuNPs such as hydrodynamic size, grafting density, hydrophilicity, colloidal stability, and biocompatibility are determined intensively. The looped polymer topology can remarkably alter physicochemical properties of polymer brushes compared with the linear counterparts. When the molecular weight of PEG is low (1 and 5 kDa), the looped polymer shells have smaller hydrodynamic size and lower grafting density than their linear analogues; when the molecular weight of PEG is high (10 kDa), the looped shells are much thicker and denser than the linear ones. Interestingly, the looped PEGs on AuNPs are more stable in a high-salt environment and have better hydrophilicity, which endow excellent biocompatibility, including protein resistance and cell viability. These results provide a simple approach to design polymer brushes with different topologies on AuNPs, improve the biocompatibility of hybrid AuNPs, and acquire the potential application in the biomedical field.

15.
ACS Appl Mater Interfaces ; 11(22): 19724-19733, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31083902

RESUMO

The programmable toehold-mediated DNA-strand-displacement reaction has demonstrated its extraordinary capability in driving the spherical nucleic acid assembly. Here, a facile strategy of integrating a DNA-strand-displacement-based DNA circuit with a universal spherical nucleic acid aggregate system was developed for the visible disassembly of spherical nucleic acids. This integrated system exhibited rapid colorimetric response and good sensitivity in the disassembly reaction and demonstrated its capability in the application of single nucleotide polymorphism discrimination. Moreover, an OR logic gate used for multiplex detection was constructed through combining the fixed spherical nucleic acid disassembly system with two DNA circuits. This strategy will have great potential in the fabrication of a portable low-cost DNA diagnostic kit, and it is also a very promising method to be used in other applications, such as complex DNA networks and programmable phase transformation of nanoparticle superlattices.


Assuntos
DNA Catalítico/química , Ácidos Nucleicos/química , Colorimetria , Polimorfismo de Nucleotídeo Único/genética
16.
Biosens Bioelectron ; 129: 50-57, 2019 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-30682689

RESUMO

Catalytic hairpin assembly (CHA) is a typical enzyme-free amplification strategy, in which the target can catalyze two hairpin probes to form a duplex and yield multiple outputs signal. However, the non-specific hybridization of two hairpin probes in CHA circuit usually occurred even in the absence of target, causing significant background leakage and impeding its practical applications in trace miRNA analysis. Herein, we proposed a novel heterogeneous CHA (hetero-CHA) design integrating with PDA microtube waveguide system, offering the advantages to enhance the target signal, but suppress the background leakage simultaneously. In hetero-CHA strategy, single-stranded targets are enriched nearby the surface of PDA microtube, facilitating the target-triggered CHA amplification and strand displacement reactions. In contrast, double-stranded DNA complexes formed by uncatalyzed hybridizations are isolated from PDA microtube, impeding the leakage signal. By combination with condensing enrichment effect, the proposed hetero-CHA probe exhibited high selectivity and sensitivity to miRNA target, giving a detection limit as low as 3.3 fM. More importantly, the proposed hetero-CHA probe can be applied directly to distinguish the expression of miRNA-21 in clinical serum of cancer patients (including lung, breast and pancreatic) from those of healthy human beings, favoring the cancer diagnosis and therapeutic evaluation.


Assuntos
Técnicas Biossensoriais/métodos , DNA/química , MicroRNAs/sangue , Polímero Poliacetilênico/química , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Técnicas Biossensoriais/instrumentação , Humanos , Limite de Detecção , MicroRNAs/análise , Hibridização de Ácido Nucleico/métodos
17.
Langmuir ; 34(44): 13438-13448, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30350688

RESUMO

A structurally nanoengineered antimicrobial polypeptide consisting of lysine and valine residues is a new class of antimicrobial agent with superior antibacterial activity against multidrug-resistant bacteria and low toxicity toward mammalian cells. Utilizing coarse-grained models, we studied the interactions of microbial cytoplasmic membranes with polypeptides of either (K2V1)5 (star-KV) or CM15 (star-CM15). Our computational results verify the low toxicity of polypeptides of (K2V1)5 toward the dipalmitoyl phosphatidylcholine bilayer. This low toxicity is demonstrated to originate from weakened hydrophobicity combined with its random coil conformation for (K2V1)5 because of the highly abundant valine residues, compared with the typical antimicrobial peptides, such as CM15. In the interactions with a palmitoyl-oleoyl-phosphatidylethanolamine/palmitoyl-oleoyl-phosphatidylglycerol bilayer, star-KV has greater ability in phase separation and generation of phase boundary defects not only in lipid redistribution but also in lateral dynamic movements, although both star-KV and star-CM15 can extract the phosphatidylglycerol lipids and purify the phosphatidylethanolamine lipids into continuum domains. We suggest that the polypeptide of (K2V1)5 can nondisruptively kill bacteria by hampering bacterial metabolism through reorganizing lipid domain distribution and simultaneously "freezing" lipid movement.


Assuntos
Peptídeos Catiônicos Antimicrobianos/química , Bicamadas Lipídicas/química , Sequência de Aminoácidos , Bactérias/química , Interações Hidrofóbicas e Hidrofílicas , Modelos Químicos , Simulação de Dinâmica Molecular , Nanopartículas/química , Fosfatidiletanolaminas/química , Fosfatidilgliceróis/química , Fosforilcolina/análogos & derivados , Fosforilcolina/química , Conformação Proteica
18.
Langmuir ; 34(49): 14811-14816, 2018 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-30110553

RESUMO

The synthetic DNA hybridization probe has proved its importance in biology and biotechnology. In this study, taking advantage of a novel analytical technique called dual polarization interferometry (DPI), the influence of the toehold strategy of on-chip DNA hybridization probe on the discrimination of single nucleotide polymorphism (SNP) was investigated. Through adjusting the toehold length, the toehold strategies of on-chip toehold exchange probe were thoroughly optimized. For the "6/5" probe, an optimal discrimination factor of 78% against the spurious target was achieved. Moreover, the ability of the on-chip probe in SNP discrimination was significantly enhanced compared to its pure solution counterpart. This simple and rapid detection method for SNP discrimination based on the on-chip toehold exchange probe will show great potential in disease diagnosis.


Assuntos
Sondas de DNA/química , DNA/análise , Polimorfismo de Nucleotídeo Único , DNA/genética , Sondas de DNA/genética , Ácidos Nucleicos Imobilizados/química , Interferometria/instrumentação , Interferometria/métodos , Dispositivos Lab-On-A-Chip , Hibridização de Ácido Nucleico
19.
J Am Chem Soc ; 140(31): 9979-9985, 2018 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-29999319

RESUMO

Versatile building blocks are essential for building complex and scaled-up DNA circuits. In this study, we propose a conceptually new scalable architecture called a "junction substrate" (J-substrate) that is linked by prepurified double-stranded DNA molecules. As a proof-of-concept, this novel type of substrate has been utilized to build multi-input DNA circuits, offering several advantages over the conventional substrate (referred to as a "linear substrate", L-substrate). First, the J-substrate does not require long DNA strands, thus avoiding significant synthetic errors and costs. Second, the traditional PAGE purification method is technically facilitated to obtain high-purity substrates, whereby the initial leakage is effectively eliminated. Third, the asymptotic leakage is eliminated by introducing the "junction". Finally, circuits with the optimized J-substrate architecture exhibit fast kinetics. We believe that the proposed architecture constitutes a sophisticated chassis for constructing complex circuits.


Assuntos
DNA/química , Eletroforese em Gel de Poliacrilamida , Estudo de Prova de Conceito
20.
Spectrochim Acta A Mol Biomol Spectrosc ; 204: 180-187, 2018 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-29933153

RESUMO

Aptamers could be used to construct simple and effective biosensor because the conformational switch of aptamer upon target binding is easy to be transferred to optical or electrochemical signals. Nevertheless, we found that the binding between saxitoxin (STX) and aptamer (M-30f) is not accompanied with conformational switch. Here, the circular dichroism spectra, fluorophore and quencher labeled aptamer, and crystal violet-based assays were used to identify the binding way between STX and aptamer. The results show that the conformation of aptamer is stabilized in PBS buffer (10 mM phosphate buffer, 2.7 mM KCl, 137 mM NaCl, pH 7.4) and this conformation may provide an exactly suitable cave for STX binding. Through the analysis of UV-melting curves and circular dichroism-melting curves, it is found that different concentrations of STX produce different unfolding extents of the aptamer under high temperature. Then, a simple temperature-assisted "turn-on" fluorescent aptasensor was developed to detect STX and the application in real sample detection demonstrates its feasibility. The proposed method provides not only an alternative for STX detection but also a strategy for simple aptasensor design using aptamers that do not switch conformation upon targets binding.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Técnicas Biossensoriais/métodos , Corantes Fluorescentes/metabolismo , Saxitoxina/análise , Saxitoxina/metabolismo , Aptâmeros de Nucleotídeos/química , Corantes Fluorescentes/química , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , Saxitoxina/química
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