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1.
Proc Natl Acad Sci U S A ; 120(32): e2302151120, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37523553

RESUMO

Polyelectrolyte complexation plays an important role in materials science and biology. The internal structure of the resultant polyelectrolyte complex (PEC) phase dictates properties such as physical state, response to external stimuli, and dynamics. Small-angle scattering experiments with X-rays and neutrons have revealed structural similarities between PECs and semidilute solutions of neutral polymers, where the total scattering function exhibits an Ornstein-Zernike form. In spite of consensus among different theoretical predictions, the existence of positional correlations between polyanion and polycation charges has not been confirmed experimentally. Here, we present small-angle neutron scattering profiles where the polycation scattering length density is matched to that of the solvent to extract positional correlations among anionic monomers. The polyanion scattering functions exhibit a peak at the inverse polymer screening radius of Coulomb interactions, q* ≈ 0.2 Å-1. This peak, attributed to Coulomb repulsions between the fragments of polyanions and their attractions to polycations, is even more pronounced in the calculated charge scattering function that quantifies positional correlations of all polymer charges within the PEC. Screening of electrostatic interactions by adding salt leads to the gradual disappearance of this correlation peak, and the scattering functions regain an Ornstein-Zernike form. Experimental scattering results are consistent with those calculated from the random phase approximation, a scaling analysis, and molecular simulations.

2.
Proc Natl Acad Sci U S A ; 119(32): e2203483119, 2022 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-35925890

RESUMO

Many biopolymers are highly charged, and as in the case of many polymer mixtures, they tend to phase separate as a natural consequence of chain connectivity and an associated relatively low entropy of polymer mixing. Recently, it has become appreciated that the phase-separated structures formed by such polyelectrolyte blends, called "complex coacervates," underlie numerous biological structures and processes essential to living systems, and there has been intense interest in understanding the unique physical features of this type of phase-separation process. In the present work, we are particularly concerned with the field responsiveness of stabilized coacervate droplets formed after the phase separation of polyelectrolyte blend solution and then exposed to deionized water, making the droplet interfacial layer acquire a viscoelastic character that strongly stabilizes it against coalescence. We show that we can precisely control the positions of individual droplets and arrays of them with relatively low-voltage electric fields (on the order of 10 V/cm) and that the imposition of an oscillatory field gives rise to chain formation with coarsening of these chains into long fibers. Such a phase-separation-like process is generally observed in electrorheological fluids of solid colloidal particles subjected to much larger field strengths. The key to these coacervates' electrorheological properties is the altered interfacial viscoelastic properties when the droplets are introduced into deionized water and the associated high polarizability of the droplets, similar to the properties of many living cells. Since many different molecular payloads can be incorporated into these stable droplets, we anticipate many applications.

3.
Proc Natl Acad Sci U S A ; 119(42): e2209044119, 2022 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-36227917

RESUMO

Despite continuing advances in the development of novel cellular-, antibody-, and chemotherapeutic-based strategies to enhance immune reactivity, the presence of regulatory T cells (Treg cells) remains a complicating factor for their clinical efficacy. To overcome dosing limitations and off-target effects from antibody-based Treg cell deletional strategies or small molecule drugging, we investigated the ability of hydrocarbon stapled alpha-helical (SAH) peptides to target FOXP3, the master transcription factor regulator of Treg cell development, maintenance, and suppressive function. Using the crystal structure of the FOXP3 homodimer as a guide, we developed SAHs in the likeness of a portion of the native FOXP3 antiparallel coiled-coil homodimerization domain (SAH-FOXP3) to block this key FOXP3 protein-protein interaction (PPI) through molecular mimicry. We describe the design, synthesis, and biochemical evaluation of single- and double-stapled SAHs covering the entire coiled-coil expanse. We show that lead SAH-FOXP3s bind FOXP3, are cell permeable and nontoxic to T cells, induce dose-dependent transcript and protein level alterations of FOXP3 target genes, impede Treg cell function, and lead to Treg cell gene expression changes in vivo consistent with FOXP3 dysfunction. These results demonstrate a proof of concept for rationally designed FOXP3-directed peptide therapeutics that could be used as approaches to amplify endogenous immune responsiveness.


Assuntos
Fatores de Transcrição Forkhead , Linfócitos T Reguladores , Fatores de Transcrição Forkhead/metabolismo , Regulação da Expressão Gênica , Peptídeos/metabolismo , Conformação Proteica em alfa-Hélice
4.
Chembiochem ; 25(8): e202300831, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38408302

RESUMO

Peptide and protein nanostructures with tunable structural features, multifunctionality, biocompatibility and biomolecular recognition capacity enable development of efficient targeted drug delivery tools for precision medicine applications. In this review article, we present various techniques employed for the synthesis and self-assembly of peptides and proteins into nanostructures. We discuss design strategies utilized to enhance their stability, drug-loading capacity, and controlled release properties, in addition to the mechanisms by which peptide nanostructures interact with target cells, including receptor-mediated endocytosis and cell-penetrating capabilities. We also explore the potential of peptide and protein nanostructures for precision medicine, focusing on applications in personalized therapies and disease-specific targeting for diagnostics and therapeutics in diseases such as cancer.


Assuntos
Nanoestruturas , Medicina de Precisão , Sistemas de Liberação de Medicamentos/métodos , Peptídeos/química , Nanoestruturas/uso terapêutico , Nanoestruturas/química , Preparações Farmacêuticas
5.
Bioconjug Chem ; 35(3): 300-311, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38377539

RESUMO

The unique and precise capabilities of proteins are renowned for their specificity and range of application. Effective mimicking of protein-binding offers enticing potential to direct their abilities toward useful applications, but it is nevertheless quite difficult to realize this characteristic of protein behavior in a synthetic material. Here, we design, synthesize, and evaluate experimentally and computationally a series of multicomponent phosphate-binding peptide amphiphile micelles to derive design insights into how protein binding behavior translates to synthetic materials. By inserting the Walker A P-loop binding motif into this peptide synthetic material, we successfully implemented the protein-binding design parameters of hydrogen-bonding and electrostatic interaction to bind phosphate completely and selectively in this highly tunable synthetic platform. Moreover, in this densely arrayed peptide environment, we use molecular dynamics simulations to identify an intriguing mechanistic shift of binding that is inaccessible in traditional proteins, introducing two corresponding new design elements─flexibility and minimization of the loss of entropy due to ion binding, in protein-analogous synthetic materials. We then translate these new design factors to de novo peptide sequences that bind phosphate independent of protein-extracted sequence or conformation. Overall, this work reveals that traditional complex conformational restrictions of binding by proteins can be replaced and repurposed in a multicomponent peptide amphiphile synthetic material, opening up opportunities for future enhanced protein-inspired design.


Assuntos
Fosfatos , Proteínas , Ligação Proteica , Fosfatos/química , Proteínas/química , Peptídeos/química , Sequência de Aminoácidos , Conformação Proteica
6.
Biomacromolecules ; 25(5): 2838-2851, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38567844

RESUMO

A comprehensive study focusing on the combined influence of the charge sequence pattern and the type of positively charged amino acids on the formation of secondary structures in sequence-specific polyampholytes is presented. The sequences of interest consisting exclusively of ionizable amino acids (lysine, K; arginine, R; and glutamic acid, E) are (EKEK)5, (EKKE)5, (ERER)5, (ERRE)5, and (EKER)5. The stability of the secondary structure was examined at three pH values in the presence of urea and NaCl. The results presented here underscore the combined prominent effects of the charge sequence pattern and the type of positively charged monomers on secondary structure formation. Additionally, (ERRE)5 readily aggregated across a wide range of pH. In contrast, sequences with the same charge pattern, (EKKE)5, as well as the sequences with the equivalent amino acid content, (ERER)5, exhibited no aggregate formation under equivalent pH and concentration conditions.


Assuntos
Arginina , Lisina , Lisina/química , Arginina/química , Concentração de Íons de Hidrogênio , Ureia/química
7.
Proc Natl Acad Sci U S A ; 118(50)2021 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-34880134

RESUMO

Vascular disease is a leading cause of morbidity and mortality in the United States and globally. Pathological vascular remodeling, such as atherosclerosis and stenosis, largely develop at arterial sites of curvature, branching, and bifurcation, where disturbed blood flow activates vascular endothelium. Current pharmacological treatments of vascular complications principally target systemic risk factors. Improvements are needed. We previously devised a targeted polyelectrolyte complex micelle to deliver therapeutic nucleotides to inflamed endothelium in vitro by displaying the peptide VHPKQHR targeting vascular cell adhesion molecule 1 (VCAM-1) on the periphery of the micelle. This paper explores whether this targeted nanomedicine strategy effectively treats vascular complications in vivo. Disturbed flow-induced microRNA-92a (miR-92a) has been linked to endothelial dysfunction. We have engineered a transgenic line (miR-92aEC-TG /Apoe-/- ) establishing that selective miR-92a overexpression in adult vascular endothelium causally promotes atherosclerosis in Apoe-/- mice. We tested the therapeutic effectiveness of the VCAM-1-targeting polyelectrolyte complex micelles to deliver miR-92a inhibitors and treat pathological vascular remodeling in vivo. VCAM-1-targeting micelles preferentially delivered miRNA inhibitors to inflamed endothelial cells in vitro and in vivo. The therapeutic effectiveness of anti-miR-92a therapy in treating atherosclerosis and stenosis in Apoe-/- mice is markedly enhanced by the VCAM-1-targeting polyelectrolyte complex micelles. These results demonstrate a proof of concept to devise polyelectrolyte complex micelle-based targeted nanomedicine approaches treating vascular complications in vivo.


Assuntos
Aterosclerose/metabolismo , Células Endoteliais/metabolismo , MicroRNAs/metabolismo , Animais , Aterosclerose/genética , Corantes Fluorescentes , Regulação da Expressão Gênica , Humanos , Inflamação , Masculino , Camundongos , Camundongos Knockout para ApoE , Camundongos Transgênicos , Micelas , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Farmacologia em Rede , Polieletrólitos , Regulação para Cima , Molécula 1 de Adesão de Célula Vascular
8.
Chem Rev ; 121(15): 9450-9501, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34213328

RESUMO

The structure, chemistry, and charge of interfaces between materials and aqueous fluids play a central role in determining properties and performance of numerous water systems. Sensors, membranes, sorbents, and heterogeneous catalysts almost uniformly rely on specific interactions between their surfaces and components dissolved or suspended in the water-and often the water molecules themselves-to detect and mitigate contaminants. Deleterious processes in these systems such as fouling, scaling (inorganic deposits), and corrosion are also governed by interfacial phenomena. Despite the importance of these interfaces, much remains to be learned about their multiscale interactions. Developing a deeper understanding of the molecular- and mesoscale phenomena at water/solid interfaces will be essential to driving innovation to address grand challenges in supplying sufficient fit-for-purpose water in the future. In this Review, we examine the current state of knowledge surrounding adsorption, reactivity, and transport in several key classes of water/solid interfaces, drawing on a synergistic combination of theory, simulation, and experiments, and provide an outlook for prioritizing strategic research directions.

9.
J Synchrotron Radiat ; 29(Pt 3): 721-731, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35511005

RESUMO

Bayesian-inference-based approaches, in particular the random-walk Markov Chain Monte Carlo (MCMC) method, have received much attention recently for X-ray scattering analysis. Hamiltonian MCMC, a state-of-the-art development in the field of MCMC, has become popular in recent years. It utilizes Hamiltonian dynamics for indirect but much more efficient drawings of the model parameters. We described the principle of the Hamiltonian MCMC for inversion problems in X-ray scattering analysis by estimating high-dimensional models for several motivating scenarios in small-angle X-ray scattering, reflectivity, and X-ray fluorescence holography. Hamiltonian MCMC with appropriate preconditioning can deliver superior performance over the random-walk MCMC, and thus can be used as an efficient tool for the statistical analysis of the parameter distributions, as well as model predictions and confidence analysis.

10.
Biomacromolecules ; 23(9): 3798-3809, 2022 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-35969881

RESUMO

A comprehensive study focusing on the influence of the sequence charge pattern on the secondary structure preferences of annealed polyampholytes and their responsiveness to external stimuli is presented. Two sequences are designed composed entirely of ionizable amino acids (charge fraction, f = 1) and an equal number of positive and negative charges (f+ = f- = 0.5) with distinct charge patterns consisting of lysine and glutamic acid monomers. The study reveals that the sequence charge pattern has a significant influence on the secondary structure preferences of polyampholytes at physiological pH. Furthermore, it shows that external stimuli such as pH, ionic strength, and solvent dielectric constant can be used to modulate the secondary structure of the two studied sequences. The observed secondary structure transformations for the two sequences are also substantially different from those determined for uniformly charged homo-polypeptides under matching conditions.


Assuntos
Peptídeos , Peptídeos/química , Estrutura Secundária de Proteína , Solventes
11.
J Electrochem Soc ; 169(5)2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35599744

RESUMO

DNAs have been used as probes for nanopore sensing of noncharged biomacromolecules due to its negative phosphate backbone. Inspired by this, we explored the potential of diblock synthetic polyelectrolytes as more flexible and inexpensive nanopore sensing probes by investigating translocation behaviors of PEO-b-PSS and PEO-b-PVBTMA through commonly used alpha-hemolysin (α-HL) and Mycobacterium smegmatis porin A (MspA) nanopores. Translocation recordings in different configurations of pore orientation and testing voltage indicated efficient PEO-b-PSS translocations through α-HL and PEO-b-PVBTMA translocations through MspA. This work provides insight into synthetic polyelectrolyte-based probes to expand probe selection and flexibility for nanopore sensing.

12.
J Am Chem Soc ; 143(11): 4440-4450, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33721492

RESUMO

With rising consumer demands, society is tapping into wastewater as an innovative source to recycle depleting resources. Novel reclamation technologies have been recently explored for this purpose, including several that optimize natural biological processes for targeted reclamation. However, this emerging field has a noticeable dearth of synthetic material technologies that are programmed to capture, release, and recycle specified targets; and of the novel materials that do exist, synthetic platforms incorporating biologically inspired mechanisms are rare. We present here a prototype of a materials platform utilizing peptide amphiphiles that has been molecularly engineered to sequester, release, and reclaim phosphate through a stimuli-responsive pH trigger, exploiting a protein-inspired binding mechanism that is incorporated directly into the self-assembled material network. This material is able to harvest and controllably release phosphate for multiple cycles of reuse, and it is selective over nitrate and nitrite. We have determined by simulations that the binding conformation of the peptide becomes constrained in the dense micelle corona at high pH such that phosphate is expelled when it otherwise would be preferentially bound. However, at neutral pH, this dense structure conversely employs multichain binding to further stabilize phosphate when it would otherwise be unbound, opening opportunities for higher-order conformational binding design to be engineered into this controllably packed corona. With this work, we are pioneering a new platform to be readily altered to capture other valuable targets, presenting a new class of capture and release materials for recycling resources on the nanoscale.


Assuntos
Peptídeos/química , Fosfatos/química , Sítios de Ligação , Modelos Moleculares , Estrutura Molecular
13.
Langmuir ; 37(45): 13346-13352, 2021 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-34730362

RESUMO

Using a surface forces apparatus (SFA), we have studied the nanomechanical behavior of short single-stranded and partially and fully double-stranded DNA molecules attached via one end to a self-assembled monolayer on a gold surface. Our results confirm the previously proposed "mushroom-like" polymer structure for surface-attached, single-stranded DNA at low packing density and a "brush-like" structure for the same construct at higher density. At low density we observe a transition to "rigid rod" behavior upon addition of DNA complementary to the surface-attached single strand as the fraction of molecules that are double-stranded increases, with a concomitant increase in the SFA-observed thickness of the monolayer and the characteristic length of the observed repulsive forces. At higher densities, in contrast, this transition is effectively eliminated, presumably because the single-stranded state is already extended in its "brush" state. Taken together, these studies offer insights into the structure and physics of surface-attached short DNAs, providing new guidance for the rational design of DNA-modified functional surfaces.


Assuntos
DNA , Ouro , DNA/genética , DNA de Cadeia Simples , Polímeros
14.
Soft Matter ; 16(4): 983-989, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31851201

RESUMO

The structure and dynamics of lipid membranes in the presence of extracellular macromolecules are critical for cell membrane functions and many pharmaceutical applications. The pathogen virulence-suppressing end-phosphorylated polyethylene glycol (PEG) triblock copolymer (Pi-ABAPEG) markedly changes the interactions with lipid vesicle membranes and prevents PEG-induced vesicle phase separation in contrast to the unphosphorylated copolymer (ABAPEG). Pi-ABAPEG weakly absorbs on the surface of lipid vesicle membranes and slightly changes the structure of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) unilamellar vesicles at 37 °C, as evidenced by small angle neutron scattering. X-ray reflectivity measurements confirm the weak adsorption of Pi-ABAPEG on DMPC monolayer, resulting in a more compact DMPC monolayer structure. Neutron spin-echo results show that the adsorption of Pi-ABAPEG on DMPC vesicle membranes increases the membrane bending modulus κ.


Assuntos
Membrana Celular/química , Bicamadas Lipídicas/química , Lipídeos de Membrana/química , Fosfatidilcolinas/química , Membrana Celular/ultraestrutura , Dimiristoilfosfatidilcolina/química , Glicerilfosforilcolina/química , Humanos , Bicamadas Lipídicas/metabolismo , Polietilenoglicóis/química , Polímeros/química , Espalhamento a Baixo Ângulo , Lipossomas Unilamelares/química , Lipossomas Unilamelares/metabolismo
16.
Molecules ; 25(11)2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32486282

RESUMO

A series of model polyelectrolyte complex micelles (PCMs) was prepared to investigate the consequences of neutral and zwitterionic chemistries and distinct charged cores on the size and stability of nanocarriers. Using aqueous reversible addition-fragmentation chain transfer (RAFT) polymerization, we synthesized a well-defined diblock polyelectrolyte system, poly(2-methacryloyloxyethyl phosphorylcholine methacrylate)-block-poly((vinylbenzyl) trimethylammonium) (PMPC-PVBTMA), at various neutral and charged block lengths to compare directly against PCM structure-property relationships centered on poly(ethylene glycol)-block-poly((vinylbenzyl) trimethylammonium) (PEG-PVBTMA) and poly(ethylene glycol)-block-poly(l-lysine) (PEG-PLK). After complexation with a common polyanion, poly(sodium acrylate), the resulting PCMs were characterized by dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). We observed uniform assemblies of spherical micelles with a diameter ~1.5-2× larger when PMPC-PVBTMA was used compared to PEG-PLK and PEG-PVBTMA via SAXS and DLS. In addition, PEG-PLK PCMs proved most resistant to dissolution by both monovalent and divalent salt, followed by PEG-PVBTMA then PMPC-PVBTMA. All micelle systems were serum stable in 100% fetal bovine serum over the course of 8 h by time-resolved DLS, demonstrating minimal interactions with serum proteins and potential as in vivo drug delivery vehicles. This thorough study of the synthesis, assembly, and characterization of zwitterionic polymers in PCMs advances the design space for charge-driven micelle assemblies.


Assuntos
Polieletrólitos/química , Polietilenoglicóis/química , Polímeros/química , Difusão Dinâmica da Luz , Micelas , Espalhamento a Baixo Ângulo , Difração de Raios X
17.
Langmuir ; 35(48): 15564-15572, 2019 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-31414810

RESUMO

Polyelectrolyte brushes consist of charged polymer chains attached on one end to a surface at high densities. They are relevant for many practical applications ranging from biosensors to drug delivery to colloidal stability. Their structure and functionality can be dramatically influenced by multivalent counterions in the solution environment. In this work, the surface forces apparatus (SFA) and atomic force microscopy (AFM) were used to investigate the effects of three alkaline earth divalent cations, Mg2+, Ca2+, and Ba2+, on the structures of polystyrenesulfonate (PSS) brushes tethered to mica and silicon oxide surfaces. While all these ions caused significant shrinkage of the height of the PSS brushes, strong ion-specific effects were observed. Mg2+ and Ca2+ caused homogeneous shrinkage; Ba2+ led to pinned-micelle like inhomogeneous structures. Isothermal titration calorimetry (ITC) demonstrated that this ion specificity was mainly caused by the difference in binding energy between sulfonate groups and the divalent cations. Considering the abundance of divalent cations in industrial processes, natural environments, and biological systems, the understanding of strong ion-specific effects of divalent counterions is of great importance for theoretical studies and various applications involving polyelectrolytes.

18.
Langmuir ; 35(5): 1699-1713, 2019 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29641904

RESUMO

There is a need for the development of antifouling materials to resist adsorption of biomacromolecules. Here we describe the preparation of a novel zwitterionic block copolymer with the potential to prevent or delay the formation of microbial biofilms. The block copolymer comprised a zwitterionic (hydrophilic) section of alternating glutamic acid (negatively charged) and lysine (positively charged) units and a hydrophobic polystyrene section. Cryo-TEM and dynamic-light-scattering (DLS) results showed that, on average, the block copolymer self-assembled into 7-nm-diameter micelles in aqueous solutions (0 to 100 mM NaCl, pH 6). Quartz crystal microbalance with dissipation monitoring (QCM-D), atomic force microscopy (AFM), and contact angle measurements demonstrated that the block copolymer self-assembled into a brush-like monolayer on polystyrene surfaces. The brush-like monolayer produced from a 100 mg/L block copolymer solution exhibited an average distance, d, of approximately 4-8 nm between each block copolymer molecule (center to center). Once the brush-like monolayer self-assembled, it reduced EPS adsorption onto the polystyrene surface by ∼70% (mass), reduced the rate of bacterial attachment by >80%, and inhibited the development of thick biofilms. QCM-D results revealed that the EPS molecules penetrate between the chains of the brush and adsorb onto the polystyrene surface. Additionally, AFM analyses showed that the brush-like monolayer prevents the adhesion of large (> d) hydrophilic colloids onto the surface via hydration repulsion; however, molecules or colloids small enough to fit between the brush polymers (< d) were able to be adsorbed onto the surface via van der Waals interactions. Overall, we found that the penetration of extracellular organelles, as well as biopolymers through the brush, is critical for the failure of the antifouling coating, and likely could be prevented through tuning of the brush density. Stability and biofilm development testing on multiple surfaces (polypropylene, glass, and stainless steel) support practical applications of this novel block copolymer.


Assuntos
Incrustação Biológica/prevenção & controle , Materiais Revestidos Biocompatíveis/química , Ácido Poliglutâmico/análogos & derivados , Polilisina/análogos & derivados , Adsorção , Biofilmes/efeitos dos fármacos , Micelas , Ácido Poliglutâmico/química , Polilisina/química , Poliestirenos/química , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/fisiologia
19.
Langmuir ; 35(52): 17082-17089, 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31790593

RESUMO

Cysteine-based polyzwitterionic brushes have been prepared via a two-step route. First, poly(allyl methacrylate) (PAMA) brushes have been grown from the surface of silicon substrates using surface-initiated atom transfer radical polymerization. The obtained PAMA brushes with free pendant vinyl groups were further modified via radical thiol-ene addition reaction to attach l-cysteine moieties. Surface ζ potential investigations on pH-responsiveness of these poly(cysteine methacrylate) (PCysMA) brushes confirm their zwitterionic character at intermediate pH range, while at pH values either below pH 3.50 or above pH 8.59, they exhibit polyelectrolyte character. Under acid (pH < 3.50) or base (pH > 8.59) conditions, they possess either cationic or anionic character, respectively. In the zwitterionic region, these PCysMA brushes show positive surface ζ potential in the presence of Pb(CH3COO)2 solutions of various concentrations. The results are in line with microscopic investigations using anomalous X-ray reflectivity (AXRR) carried out along the absorption edge of Pb2+ ions. When the photon energies were varied around the absorption L3 edge of lead (13037 eV), the Pb2+ concentration normal to the silicon substrates, as a function of depth inside PCysMA brushes, could be revealed at the nanoscale. Both ζ potential and AXRR measurements confirm the enrichment of Pb2+ ions inside PCysMA brushes, indicating the potential of PCysMA to be used as a water purification material.

20.
Nano Lett ; 18(11): 7111-7117, 2018 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-30339032

RESUMO

Polyelectrolyte complex micelles (PCMs), nanoparticles formed by electrostatic self-assembly of charged polymers with charged-neutral hydrophilic block copolymers, offer a potential solution to the challenging problem of delivering therapeutic nucleic acids into cells and organisms. Promising results have been reported in vitro and in animal models but basic structure-property relationships are largely lacking, and some reports have suggested that double-stranded nucleic acids cannot form PCMs due to their high bending rigidity. This letter reports a study of PCMs formed by DNA oligonucleotides of varied length and hybridization state and poly(l)lysine-poly(ethylene glycol) block copolymers with varying block lengths. We employ a multimodal characterization strategy combining small-angle X-ray scattering (SAXS), multiangle light scattering (MALS), and cryo-electron microscopy (cryo-TEM) to simultaneously probe the morphology and internal structure of the micelles. Over a wide range of parameters, we find that nanoparticle shape is controlled primarily by the hybridization state of the oligonucleotides with single-stranded oligonucleotides forming spheroidal micelles and double-stranded oligonucleotides forming wormlike micelles. The length of the charged block controls the radius of the nanoparticle, while oligonucleotide length appears to have little impact on either size or shape. At smaller length scales, we observe parallel packing of DNA helices inside the double-stranded nanoparticles, consistent with results from condensed genomic DNA. We also describe salt- and thermal-annealing protocols for preparing PCMs with high repeatability and low polydispersity. Together, these results provide a capability to rationally design PCMs with desired sizes and shapes that should greatly assist development of this promising delivery technology.


Assuntos
Micelas , Nanopartículas/química , Oligonucleotídeos/química , Polieletrólitos/química , Nanopartículas/ultraestrutura , Tamanho da Partícula , Polietilenoglicóis/química , Polilisina/química , Relação Estrutura-Atividade
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