Here we have investigated the effect of enshrouding polymer-coated nanoparticles (NPs) with polyethylene glycol (PEG) on the adsorption of proteins and uptake by cultured cells. PEG was covalently ...linked to the polymer surface to the maximal grafting density achievable under our experimental conditions. Changes in the effective hydrodynamic radius of the NPs upon adsorption of human serum albumin (HSA) and fibrinogen (FIB) were measured in situ using fluorescence correlation spectroscopy. For NPs without a PEG shell, a thickness increase of around 3 nm, corresponding to HSA monolayer adsorption, was measured at high HSA concentration. Only 50% of this value was found for NPs with PEGylated surfaces. While the size increase clearly reveals formation of a protein corona also for PEGylated NPs, fluorescence lifetime measurements and quenching experiments suggest that the adsorbed HSA molecules are buried within the PEG shell. For FIB adsorption onto PEGylated NPs, even less change in NP diameter was observed. In vitro uptake of the NPs by 3T3 fibroblasts was reduced to around 10% upon PEGylation with PEG chains of 10 kDa. Thus, even though the PEG coatings did not completely prevent protein adsorption, the PEGylated NPs still displayed a pronounced reduction of cellular uptake with respect to bare NPs, which is to be expected if the adsorbed proteins are not exposed on the NP surface.
Background
Swirling flow, organized in vortices, contributes to adequate left ventricular function. In this study, we apply a novel echocardiographic flow‐mapping technique, vector flow mapping ...(VFM), to evaluate the main characteristics of left ventricular vortices and its relation to filling parameters.
Methods
Forty‐eight subjects underwent conventional transthoracic echocardiographic examination with additional intracardiac flow assessment with VFM using a Aloka Alpha‐10 system and experimental VFM analysis software. To analyze vortex behavior, its rotation direction, duration, location inside the left ventricle, size, and intensity were assessed in apical long‐axis view. Its relation to conventional left ventricular filling parameters was then analyzed.
Results
Two vortex components were consistently identified following each transmitral filling wave. The anterior component of these visualized vortices was analyzed, due to its higher significance in the cardiac cycle, following early filling (V1) and atrial contraction (V2). Differences were observed in several aspects of vortex behavior between V1 and V2, particularly in patients with normal left ventricular filling parameters. These differences may be related to varying roles of vortices in different periods of the cardiac cycle.
Conclusions
Vector flow mapping allowed visualization and measurement of several parameters defining vortex behavior inside the cardiac cycle. The differences observed in these parameters between vortices in different phases of the cardiac cycle may be related to their role in optimizing cardiac function.
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Naturally occurring antimicrobial peptides (AMPs) hold promise as future therapeutics against multidrug resistant microorganisms. Recently, we have discovered that a derivative of the ...frog skin AMP esculentin-1a, Esc(1-21), is highly potent against both free living and biofilm forms of the bacterial pathogen Pseudomonas aeruginosa. However, bringing AMPs into clinics requires to overcome their low stability, high toxicity and inefficient delivery to the target site at high concentrations. Importantly, peptide conjugation to gold nanoparticles (AuNPs), which are among the most applied inorganic nanocarriers in biomedical sciences, represents a valuable strategy to solve these problems. Here we report that covalent conjugation of Esc(1-21) to soluble AuNPs AuNPs@Esc(1-21) via a poly(ethylene glycol) linker increased by ∼15-fold the activity of the free peptide against the motile and sessile forms of P. aeruginosa without being toxic to human keratinocytes. Furthermore, AuNPs@Esc(1-21) resulted to be significantly more resistant to proteolytic digestion and to disintegrate the bacterial membrane at very low concentration (5nM). Finally, we demonstrated for the first time the capability of peptide-coated AuNPs to display a wound healing activity on a keratinocytes monolayer. Overall, these findings suggest that our engineered AuNPs can serve as attractive novel biological-derived material for topical treatment of epithelial infections and healing of the injured tissue.
Despite conjugation of AMPs to AuNPs represents a worthwhile solution to face some limitations for their development as new therapeutics, only a very limited number of studies is available on peptide-coated AuNPs. Importantly, this is the first report showing that a covalent binding of a linear AMP via a poly(ethylene glycol) linker to AuNPs highly enhances antipseudomonal activity, preserving the same mode of action of the free peptide, without being harmful. Furthermore, AuNPs@Esc(1-21) are expected to accelerate recovery of an injured skin layer. All together, these findings suggest our peptide-coated AuNPs as attractive novel nanoscale formulation to treat bacterial infections and to heal the injured tissue.
Magnetic resonance based molecular imaging has emerged as a very promising technique for early detection and treatment of a wide variety of diseases, including cancer, neurodegenerative disorders, ...and vascular diseases. The limited sensitivity and specificity of conventional MRI are being overcome by the development of a new generation of contrast agents, using nanotechnology approaches, with improved magnetic and biological properties. In particular, for molecular imaging, high specificity, high sensitivity, and long blood circulation times are required. Furthermore, the lack of toxicity and immunogenicity together with low-cost scalable production are also necessary to get them into the clinics. In this work, we describe a facile, robust and cost-effective ligand-exchange method to synthesize dual T1 and T2 MRI contrast agents with long circulation times. These contrast agents are based on manganese ferrite nanoparticles (MNPs) between 6 and 14 nm in size covered by a 3 kDa polyethylene glycol (PEG) shell that leads to a great stability in aqueous media with high crystallinity and magnetization values, thus retaining the magnetic properties of the uncovered MNPs. Moreover, the PEGylated MNPs have shown different relaxivities depending on their size and the magnetic field applied. Thus, the 6 nm PEGylated MNPs are characterized by a low r2/r1 ratio of 4.9 at 1.5 T, hence resulting in good dual T1 and T2 contrast agents under low magnetic fields, whereas the 14 nm MNPs behave as excellent T2 contrast agents under high magnetic fields (r2 = 335.6 mM(-1) s(-1)). The polymer core shell of the PEGylated MNPs minimizes their cytotoxicity, and allows long blood circulation times. This combination of cellular compatibility and excellent T2 and r2/r1 values under low magnetic fields, together with long circulation times, make these nanomaterials very promising contrast agents for molecular imaging.
Europium-doped calcium hydroxyapatite and fluoroapatite nanophosphors functionalized with poly(acrylic acid) (PAA) have been synthesized through a one-pot microwave-assisted hydrothermal method from ...aqueous basic solutions containing calcium nitrate, sodium phosphate monobasic, and PAA, as well as sodium fluoride in the case of the fluoroapatite particles. In both cases a spindlelike morphology was obtained, resulting from an aggregation process of smaller subunits which also gave rise to high specific surface area. The size of the nanospindles was 191 (32) × 40 (5) nm for calcium hydroxyapatite and 152 (24) × 38 (6) nm for calcium fluoroapatite. The luminescent nanoparticles showed the typical red luminescence of Eu3+, which was more efficient for the fluoroapatite particles than for the hydroxyapatite. This is attributed to the presence of OH– quenchers in the latter. The nanophosphors showed negligible toxicity for Vero cells. Both PAA-functionalized nanophosphors showed a very high (up to at least 1 week) colloidal stability in 2-(N-morpholino)ethanesulfonic acid (MES) at pH 6.5, which is a commonly used buffer for physiological pH. All these features make both kinds of apatite-based nanoparticles promising tools for biomedical applications, such as luminescent biolabels and tracking devices in drug delivery systems.
High aspect ratio magnetic nanomaterials possess anisotropic properties that make them attractive for biological applications. Their elongated shape enables multivalent interactions with receptors ...through the introduction of multiple targeting units on their surface, thus enhancing cell internalization. Moreover, due to their magnetic anisotropy, high aspect ratio nanomaterials can outperform their spherical analogues as contrast agents for magnetic resonance imaging (MRI) applications. In this review, we first describe the two main synthetic routes for the preparation of anisotropic magnetic nanomaterials: (i) direct synthesis (in which the anisotropic growth is directed by tuning the reaction conditions or by using templates) and (ii) assembly methods (in which the high aspect ratio is achieved by assembly from individual building blocks). We then provide an overview of the biomedical applications of anisotropic magnetic nanomaterials: magnetic separation and detection, targeted delivery and magnetic resonance imaging.
This review highlights recent progress in the synthesis of anisotropic magnetic nanomaterials and their biomedical applications.
Superparamagnetic iron oxide-based nanoparticles (SPIONS) have attracted an enormous amount of attention for their potential use in biomedical applications, due to their good biocompatibility and low ...toxicity. The current study considers citric acid-conjugated manganese ferrite and its synergy to be used in MRI and in hyperthermia treatment, thus showing theragnostic applications. High colloidal stability was obtained with this functionalization. SPIONS with superparamagnetic behavior of crystal sizes of approximately 20 nm were obtained via an electrochemical synthesis method. One of the highest specific absorption rate (SAR) values was achieved in this work (1661 W g–1), under a magnetic field of 30 mT at 717 kHz frequency, compared with other magnetic ferrites in the literature. These nanoparticles dissipate heat through Néel relaxation and, together with the high SAR value obtained, indicate an excellent material for hyperthermia treatment of cancer. In addition, these nanoparticles exhibit transverse relaxivity behavior, with an r 2 value of 394 mM–1 s–1, i.e., at least two times higher than the value of a commercial magnetic contrast agent based on iron oxides. Finally, no toxicity effects of these nanoparticles are evidenced; as a result, these nanoparticles are appropriate for in vivo application.
A procedure for the synthesis of multifunctional europium(III)-doped gadolinium(III) fluoride (Eu:GdF3) nanoparticles (∼85 nm) with quasispherical shape by precipitation at 120 °C from diethylene ...glycol solutions containing lanthanide chlorides and an ionic liquid (1-Butyl, 2-methylimidazolium tetrafluoroborate) as fluoride source has been developed. These nanoparticles were polycrystalline and crystallized into a hexagonal structure, which is unusual for GdF3. They were also mesoporous (pore size = 3.5 Å), having a rather high BET surface area (75 m2 g–1). The luminescent and magnetic (relaxivity) properties of the Eu:GdF3 nanoparticles have been also evaluated in order to assess their potentiality as “in vitro” optical biolabels and contrast agent for magnetic resonance imaging. Finally, a procedure for their functionalization with aspartic-dextran polymers is also reported. The functionalized Eu:GdF3 nanoparticles presented negligible toxicity for Vero cells, which make them suitable for biotecnological applications.
Introduction:
Early-life educational experiences are associated with cognitive performance in aging. Early literacy seems to improve executive control mechanisms, however, it is not clear whether ...early education would still be an advantage in countries like Peru, where access to and quality of education is highly variable.
Aim:
Our objective was to analyze the association of literacy level with executive control factors.
Method:
We evaluated 93 healthy older adults with a clinical protocol that included the Mini-Mental State Examination, the Geriatric Depression Scale and Global Dementia Staging. We also used a neuropsychological executive function battery which included the Trail-Making Test parts A and B, the Stroop Test, phonological and semantic verbal fluency tasks, Forward and Backward Digits, Numbers and Letters of the Wechsler Scale, and the Go/No-Go task. We used a principal component analysis for the dimensional reduction of the variables. To measure the level of literacy we used the word accentuation test (WAT).
Results:
We observed statistically significant correlations between the principal components (PCs) of working memory, cognitive flexibility and inhibitory control with the WAT scores. Furthermore, we observed that processing speed and WAT predict the scores on PCs factors better than years of education and age.
Conclusions:
Literacy level correlates more closely with better cognitive performance than years of education and thus, might improve executive control factors that could compensate and protect against brain changes in cognitive decline and dementia.
Ln‐doped (Ln = Eu or Nd) LaVO4 nanoparticles functionalized with poly(acrylic acid) (PAA) were prepared from lanthanide and vanadate precursors in the presence of PAA by a simple one‐pot method that ...consists of a homogeneous precipitation reaction in ethylene glycol/water at a moderate temperature (120 °C). The size of the nanoparticles could be modified in the 40–70 nm range by adjusting the amount of PAA added. The effects of the Eu and Nd contents of these nanomaterials on theirs optical properties (emission intensity and lifetime) were also analyzed to find the optimum nanophosphors. Finally, the nanoparticles showed negligible cytotoxicity for Vero cells at concentrations up to 0.05 mg mL–1 and a high colloidal stability in physiological buffer solutions; therefore, they satisfy the most important requirements for in vitro biotechnological applications.
Uniform lanthanide‐doped LaVO4 nanospheres functionalized with poly(acrylic acid) are synthesized with a controllable size by a one‐pot procedure. As these nanoparticles present strong red (Eu) or near‐infrared (Nd) luminescence, are nontoxic for cells, and show high colloidal stability in physiological buffer, they are good candidates as optical biomarkers for in vitro applications.
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