Hydrophilic Probe Research Articles

High Anti-Interfering Profiling of Endogenous Glycopeptides for Human Plasma by the Dual-Hydrophilic Metal-Organic Framework.

Glycopeptidome profiling provides large-scale information about the glycosylation level of endogenous peptides, reflecting the dynamic processes of disease occurrences and developments. However, endogenous glycopeptides are usually submerged in complex fluids containing a wide variety of interference molecules, such as high concentration proteins, nonglycopeptides, and salts, which confounds attempts to identify glycopeptidome. Here, a dual-hydrophilic metal-organic framework is developed to selectively capture endogenous glycopeptides in complex biological fluid. The hydrophilic matrix material provides specific selectivity toward glycopeptides, while the deliberate surface regulation using hydrophilic species enhances its interaction with glycopeptides. This hydrophilic probe presents an extremely high performance in anti-interfering enrichment of glycopeptides from mimic complex samples, even when the molar ratio of immunoglobulin G versus bovine serum albumin was up to about 1:5000. More excitingly, in the practical application of glycopeptidome analysis, a total of 380 endogenous N-glycopeptides with 180 unique N-glycopeptide sites were identified from human plasma. This strategy is expected to broaden the application of dual-hydrophilic MOF-based materials, especially in dealing with the challenges of extremely complex biological samples.

Technology assessment of new biodegradable poly(R‐3‐hydroxybutyrate‐co‐1,4‐butylene adipate) copolymers for drug delivery

ABSTRACTNew biodegradable biomaterials are attracting a huge interest as alternative to conventional polymers used in the field of drug delivery. In this work, we evaluated the ability of new biocompatible and biodegradable polyesters to form nanoparticles (NPs), and tested their potential carrier properties for controlled release of hydrophilic or lipophilic compounds. Multiblock copolymers derived from poly(R‐3‐hydroxybutyrate) and poly(1,4‐butylene adipate) by microwave‐assisted transesterification, having different chemical and physicochemical properties were tested. Nanoprecipitation was applied to obtain NPs with a homogenous size distribution. Oil Red O and calcein were encapsulated as lipophilic and hydrophilic probes, evaluating NP mean size and size polydispersity, surface charge, encapsulation efficiency, and release profile. The release curves were fitted into mathematical models to investigate the release mechanism. NPs stability appeared to be strictly related to storage conditions. The NPs were also successfully autoclaved and their mucoadhesive behavior was assessed by a “mucin‐particle method.” © 2018 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47233.

Conversion of wood-biopolymers into macrofibers with tunable surface energy via dry-jet wet-spinning

Surface chemistry of regenerated all-wood-biopolymer fibers that are fine-tuned by composition of cellulose, lignin and xylan is elucidated via revealing their surface energy and adhesion. Xylan additive resulted in thin fibers and decreased surface energy of the fiber outer surfaces compared to the cellulose fibers, or when lignin was used as an additive. Lignin increased the water contact angle on the fiber surface and decreased adhesion force between the fiber cross section and a hydrophilic probe, confirming that lignin reduced fiber surface affinity to water. Lignin and xylan enabled fiber decoration with charged groups that could tune the adhesion force between the fiber and an AFM probe. The fibers swelled in water: the neat cellulose fiber cross section area increased 9.2%, the fibers with lignin as the main additive 9.1%, with xylan 6.8%, and the 3-component fibers 5.5%. This indicates that dimensional stability in elevated humidity is improved in the case of 3-component fiber compared to 2-component fibers. Xylan or lignin as an additive neither improved strength nor elongation at break. However, improved deformability was achieved when all the three components were incorporated into the fibers.Graphical

Hydrophilic probe in mesoporous pore for selective enrichment of endogenous glycopeptides in biological samples

As one of the most important post-translational modifications (PTMs) of peptidome, glycopeptidome is closely related to serious disease, especially to cancer. In order to specifically discover and analyze glycopeptidome biomarkers for clinical diagnosis of cancer on early-stage, it is crucial to develop efficient technique to analyze low-abundance of endogenous glycopeptides in biological samples. In this report, a hydrophilic probe in mesoporous pore (denoted as Fe3O4@mSiO2@G6P) was designed and prepared. By taking advantage of the excellent hydrophilicity and size-exclusion ability, we applied Fe3O4@mSiO2@G6P to capture glycopeptides from both horseradish peroxidase (HRP) and immunoglobulin (IgG) digests successfully. Moreover, a total of 39 and 25 endogenous glycopeptides were identified from healthy saliva and gastric saliva, respectively, indicating the great potential of this probe for the exploration of glycopeptidome biomarkers.

Hydrophilic fluorinated molecules for spectral 19F MRI

Fluorine-19 (19F) Magnetic Resonance Imaging (MRI) is an emerging modality for molecular imaging and cell tracking. The hydrophobicity of current exogenous probes, perfluorocarbons (PFCs) and perfluoropolyethers (PFPEs), limits the formulation options available for in vivo applications. Hydrophilic probes permit more formulation flexibility. Further, the broad Nuclear Magnetic Resonance (NMR) chemical shift range of organofluorine species enables multiple probes with unique 19F MR signatures for simultaneous interrogation of distinct molecular targets in vivo. We report herein a flexible approach to stable liposomal formulations of hydrophilic fluorinated molecules (each bearing numerous magnetically equivalent 19F atoms), with 19F encapsulation of up to 22.7 mg/mL and a per particle load of 3.6 × 106 19F atoms. Using a combination of such probes, we demonstrate, with no chemical shift artifacts, the simultaneous imaging of multiple targets within a given target volume by spectral 19F MRI.

Interaction of water-soluble pentaamino acid fullerene derivatives with membranes of phosphatidylcholine liposomes

Regularities of interaction of water-soluble pentaamino acid derivatives of fullerenes (WPDFs) with the lipid bilayer of phosphatidylcholine liposomes were studied using the fluorescent probe method. The studied WPDFs act as quenchers of fluorescence of the hydrophilic probe 2,7-dibromoproflavine in aqueous solutions and in the membranes of phsophatidylcholine liposomes, as well as of the hydrophobic probe pyrene in the phospholipid membrane. The singlet state of the probes is deactivated due to the formation of the long-lived WPDF—probe complex rather than their dynamic interaction. The WPDFs stud- ied were revealed to penetrate into the bilayer membrane of phosphatidylcholine liposomes. The localization of the pentaamino acid fullerene derivatives in the region of polar heads and fatty acid chains of the membrane phospholipids was established on the basis of estimation of the equilibrium constants in the WPDF—probe complexes.

Alkoxy Tetrazine Substitution at a Boron Center: A Strategy for Synthesizing Highly Fluorogenic Hydrophilic Probes.

Strongly fluorogenic boron dipyrromethene (BODIPY)-tetrazine probes have been obtained by introducing an alkoxy tetrazine fragment at the boron center. The fluorescence signal from these probes strongly increases by up to 225-fold after reaction with bioorthogonal coupling partners, and the hydrophilicity of probes is improved, such that they are suitable for live-cell imaging.

Perfusion-based fluorescence imaging method delineates diverse organs and identifies multifocal tumors using generic near-infrared molecular probes.

Rapid detection of multifocal cancer without the use of complex imaging schemes will improve treatment outcomes. In this study, dynamic fluorescence imaging was used to harness differences in the perfusion kinetics of near-infrared (NIR) fluorescent dyes to visualize structural characteristics of different tissues. Using the hydrophobic nontumor-selective NIR dye cypate, and the hydrophilic dye LS288, a high tumor-to-background contrast was achieved, allowing the delineation of diverse tissue types while maintaining short imaging times. By clustering tissue types with similar perfusion properties, the dynamic fluorescence imaging method identified secondary tumor locations when only the primary tumor position was known, with a respective sensitivity and specificity of 0.97 and 0.75 for cypate, and 0.85 and 0.81 for LS288. Histological analysis suggests that the vasculature in the connective tissue that directly surrounds the tumor was a major factor for tumor identification through perfusion imaging. Although the hydrophobic dye showed higher specificity than the hydrophilic probe, use of other dyes with different physical and biological properties could further improve the accuracy of the dynamic imaging platform to identify multifocal tumors for potential use in real-time intraoperative procedures.

Water solubility is essential for fluorescent probes to image hypochlorous acid in live cells.

We synthesised four probes and compared their HClO-detecting ability in different solvents. The data showed that only hydrophilic probes could sensitively and accurately detect HClO in live cells. Meanwhile, the addition of organic solvents, as is commonly practised, weakens the oxidising capacity of HClO and thus generates inaccurate outcomes.

Features of Behavior of Isotactic Polypropylene Films upon Pervaporation

The most important aspects of the large-tonnage synthesis of isotactic polypropylene represent a commercial secret. After polypropylene synthesis is completed, catalysts and other substances involved in the formation of the final product pass into the category of worthless and unknown impurities. This circumstance determines the peculiarities and difficulties of studying the behavior of impurities in polypropylene films. In this paper, the interaction of hydrophobic and hydrophilic probe liquids with polypropylene films (membranes) containing such impurities has been studied using pervaporation at different temperatures. The supramolecular structure of the polypropylene films has been successively modified by one- and two-sided hexane sorption. This procedure has decreased the apparent activation energy of permeability during pervaporation of water and acetone. It has been shown that, in the long run, the transmembrane convective pervaporation stream of acetone displaces hydrophobic and hydrophilic impurities from the polypropylene films.

A novel lactoferrin-modified stealth liposome for hepatoma-delivery of triiodothyronine

Triiodothyronine (T3), a thyroid hormone synthesized and secreted by the thyroid gland, plays an essential role in morphogenesis and differentiation through interaction with its nuclear receptors (TRs). However, there are increasing evidences for its role in hepatocellular carcinoma (HCC) suppression. The aim of this work was to develop an effective hepatocellular carcinoma targeting drug delivery system to improve T3 delivery to hepatic cancer cells as well as to reduce toxic side effects. Three different liposomal systems, such as unmodified, Stealth (PEGylated) and Lactoferrin (Lf)-modified-Stealth liposomes were successfully prepared by the film hydration method, and fully characterized. Liposome cell interactions and cellular uptake were evaluated in three different HCC target cells (FaO, HepG2 and SKHep) by confocal microscopy. Finally, in vitro cytotoxicity studies were carried out by using MTT assay to evaluate toxicity of the liposome delivery system and to test the effect of T3 when incorporated into liposomes. Internalization studies, performed using Lf-modified-liposomes labeled with the lipophilic marker Rho-PE and loaded with the hydrophilic probe CF, clearly demonstrated the effective internalization of both hydrophilic and lipophilic markers. Lf-liposomes might markedly enhance the specific cell binding and cellular uptake in hepatoma cells due to the mediating of Lf that could bind with high affinity to multiple receptors on cell surface, such as ASGP-R. Results obtained from this study highlight that the Lf- modified-liposomal delivery system may ensure a specific and sustained T3 delivery, thus, allowing reduced therapeutic doses and deleterious side effects of T3.

Effect of sugars on the dynamics of hydrophilic fluorophores confined inside the water pool of anionic reverse micelle: A spectroscopic approach

In this article, we have investigated the structural and chemical effects of two sugar molecules, namely sucrose and sucralose on the structure of anionic reverse micelle (RM) AOT (aerosol-OT; sodium bis(2-ethylhexyl)sulfosuccinate)/n-heptane. The artificial sugar alternative sucralose shows very unique physical properties unlike other sugar molecules including sucrose and it is the reason behind choosing these two sugars in our study. The variation of shapes and sizes of the water pool of RM in presence of the two sugar molecules are investigated using dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) measurements. It is observed that addition of both the sugar molecules swell the water pool of the RM and this enhancement is greater for sucralose. Moreover, we have employed time-correlated single photon counting (TCSPC) and fluorescence correlation spectroscopy (FCS) techniques for hydrophilic probes Coumarin 343(C343) and Rhodamine 6G (R6G) respectively inside the RM and we have observed that these two sugar molecules strongly retard the solvation and rotational dynamics of C343 and the translational diffusion of R6G inside the RM. Replacement of the smaller sized water molecules by the larger sized sugar molecules at the interface of RM through stronger hydrogen bonding with the interfacial sulfonate moiety of AOT increases the microviscosity and this may be the probable reason behind the slow dynamics of the probes in presence of sucrose. Along with this factor, strong electrostatic interaction of highly polar molecule sucralose with RM interface and with the dye molecules further retards the dynamics of fluorophores. Therefore, sucralose molecule exhibits its distinct feature by swelling the water pool inside the RM and slowing down the dynamics of the hydrophilic probes to a greater extent compared to sucrose which provides a new aspect of RM and sugar interaction.

Water dispersions of natural graphene based carbon nanoparticles: ESR spin probe study

Dynamic and phase behavior of an aqueous dispersion of shungite carbon (ShC) nanoparticles, one of natural graphene-like nanomaterials structured in a special way in an aqueous medium, is of considerable interest, as in the case of other carbon nanomaterials, due to its effects and presumable technological and biomedical applications. ShC nanoparticles in aqueous dispersions of different composition were studied in the temperature range 7–60°C using electron spin resonance (ESR) technique of stable spin probes. Hydrophobic probe 5-DOXYL stearic acid was introduced into the structure of hydrated ShC nanoparticles. Hydrophilic probe 4-oxo-TEMPO was dissolved in the surrounding bulk solvent. It is assumed that an increase in the immobilization of the hydrophobic probe in the presence of NaCl, urea, HCl, NaOH, sucrose is associated with a change in the state of hydration of ShC nanoparticles. At the same time, an increase in the carbon concentration during the evaporation of water did not cause changes in the dynamics of the probe until the nanoparticles were dehydrated. Changes in hydration of the hydrophobic probe on the ShC nanoparticles at a temperature of about 17–20°C can be associated with a change in the state of nanoparticle dispersion near the critical mixing temperature of the main and metastable phases. The sigmoid type Arrhenius dependence of the mobility of both the hydrophilic and hydrophobic probes has maximum steepness in the region of the supercritical mesophase near 37°C. The structural and dynamic variations of the dispersion associated with the change in the dynamic regime in the supercritical mesophase near the Frenkel line are discussed as a probable explanation. The data obtained are interpreted on the basis of a hypothetical phase diagram of the dispersion of fullerenes and ShC nanostructures.

Glucose-6-Phosphate-Functionalized Magnetic Microsphere as Novel Hydrophilic Probe for Specific Capture of N-Linked Glycopeptides.

Developing cost-effective approaches based on hydrophilic interaction liquid chromatography (HILIC) has been the main tendency for low-abundance glycopeptides capture before LC-MS/MS analysis. Carbohydrates with outstanding biocompatibility and hydrophilicity are ubiquitous in the kingdoms of animal and plant and could be a wonderful choice as functional groups for glycopeptides enrichment. In this work, glucose-6-phosphate, as one of the indispensable cogs in pivotal metabolic wheels of life, was chosen as functionalized groups to be grafted onto the surface of Fe3O4 microspheres via one-step surface fabrication strategy. The acquired hydrophilic Fe3O4@G6P microspheres showed superior enrichment performance for glycopeptides with high sensitivity (0.5 fmol/μL) and high selectivity (1:100) and good repeatability (10 times at least). Furthermore, the Fe3O4@G6P microspheres also exhibited enrichment ability for glycopeptides in different biosamples. A total of 243 glycopeptides assigned to 92 glycoproteins and 183 glycopeptides corresponding to 74 different glycoproteins was identified from merely 2 μL of serum and saliva, respectively.

A new method for the formulation of double nanoemulsions.

Double emulsions are very attractive systems for many reasons; the most important of these are their capacity to encapsulate hydrophilic and lipophilic molecules simultaneously in a single particle and their potentiality to protect fragile hydrophilic molecules from the continuous phase. Double emulsions represent a technology that is widely present down to the micrometer scale; however, double nanoemulsions, with their new potential applications as nanomedicines or diagnosis agents, currently present a significant challenge. In this study, we propose an original two-step approach for the fabrication of double nanoemulsions with a final size below 200 nm. The process consists of the formulation of a primary water-in-oil (w1/O) nanoemulsion by high-pressure homogenization, followed by the re-emulsification of this primary emulsion by a low-energy method to preserve the double nanostructure. Various characterization techniques were undertaken to confirm the double structure and to evaluate the encapsulation efficiency of a small hydrophilic probe in the inner aqueous droplets. Complementary fluorescence confocal and cryo-TEM microscopy experiments were conducted to characterize and confirm the double structure of the double nanoemulsion.

Pharmacokinetics of lipophilically different 3-substituted 2,2,5,5-tetramethylpyrrolidine-N-oxyl radicals frequently used as redox probes in in vivo magnetic resonance studies

3-Carboxy-, 3-carbamoyl-, 3-hydroxymethyl, and 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-N-oxyl radicals (CxP, CmP, HMP, and MCP, respectively) have been widely used as redox probes in in vivo magnetic resonance studies. Knowledge of the pharmacokinetics of these probes is essential for redox analyses. The apparent partition coefficient (Kp) of these probes at neutral pH was in the order of MCP>HMP>CmP>CxP. After these probes had been injected intravenously, their blood levels decayed in a bi-phasic manner, namely, fast decay followed by slow decay. The order of the area under the curve (AUC) was CxP»HMP>MCP≥CmP, which roughly coincided with that of Kp in the opposite direction, except for CmP. Decay in the slow phase largely affected the AUC of these probes. The reduction of these probes contributed to their decay in the slow phase. A two-compartment model analysis of blood levels, cyclic voltammetry, and magnetic resonance imaging provided the following pharmacokinetic information. The distribution of the probes between the central and peripheral compartments rapidly reached an equilibrium. In addition to lipophilicity, reduction potential may also be involved in the rate of in vivo reduction of the probes. Hydrophilic probes, such as CxP and CmP, were predominantly excreted in the urine. MCP was distributed to the peripheral tissues and then rapidly reduced. HMP was unique due to its moderate lipophilicity and slower reduction. Among the probes examined, the liver and kidney appear to be included in the central compartment in the two-compartment model analysis. MCP and HMP were rapidly distributed to the brain.

A Comparative Study of the Influence of Sugars Sucrose, Trehalose, and Maltose on the Hydration and Diffusion of DMPC Lipid Bilayer at Complete Hydration: Investigation of Structural and Spectroscopic Aspect of Lipid-Sugar Interaction.

It is well-known that sugars protect membrane structures against fusion and leakage. Here, we have investigated the interaction between different sugars (sucrose, trehalose, and maltose) and phospholipid membrane of 1,2-dimyristoyl-sn-glycero-3-phoshpocholine (DMPC) using dynamic light scattering (DLS), transmission electron microscopy (TEM), and other various spectroscopic techniques. DLS measurement reveals that the addition of sugar molecule results a significant increase of the average diameter of DMPC membrane. We have also noticed that in the presence of different sugars the rotational relaxation and solvation time of coumarin 480 (C480) and coumarin 153 (C153) surrounding DMPC membrane increases, suggesting a marked reduction of the hydration behavior at the surface of phospholipid membrane. In addition, we have also investigated the effect of sugar molecules on the lateral mobility of phospholipids. Interestingly, the relative increase in rotational, solvation and lateral diffusion is more prominent for C480 than that of C153 because of their different location in lipid bilayer. It is because of preferential location of comparatively hydrophilic probe C480 in the interfacial region of the lipid bilayer. Sugars intercalate with the phospholipid headgroup through hydrogen bonding and replace smaller sized water molecules from the membrane surface. Therefore, overall, we have monitored a comparative analysis regarding the interaction of different sugar molecules (sucrose, trehalose, and maltose) with the DMPC membrane through DLS, TEM, solvation dynamics, time-resolved anisotropy, and fluorescence correlation spectroscopy (FCS) measurements to explore the structural and spectroscopic aspect of lipid-sugar interaction.

A fully-aqueous red-fluorescent probe for selective optical sensing of Hg2+ and its application in living cells

A new red-fluorescent mercury ion sensor material is designed and synthesized, which is composed of a tweezer-shaped hydrophilic probe containing bifurcated soft-base atoms N and S coupled with 2-dicyanomethylene-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran (TCF) unit. By virtue of the strong electron-accepting nature of TCF unit (as a push–pull chromophore), this designed sensor material can selectively detect Hg2+ over various tested metal ions in a 100% aqueous medium via naked-eye and photoluminescence (PL) observations. Theoretical and time-resolved photoluminescence measurements further confirmed the selectivity and reversibility of the probe towards Hg2+ via intramolocular charge transfer mechanism in this sensor material. Moreover, the living cell tests by confocal fluorescence images of this sensor material towards Hg2+ were also investigated. Finally, distinguished absorption changes and fluorescence quenching spectral appearances allowed us to present the selective optical indicator of Hg2+ via TCF moiety for the first time.

Fluorescent Detection of 2,4-DNT and 2,4,6-TNT in Aqueous Media by Using Simple Water-Soluble Pyrene Derivatives.

Pyrene-containing water-soluble probes for the fluorescent detection of nitroaromatic compounds (NACs), such as explosive components (2,4-DNT and 2,4,6-TNT) and herbicides (2,4-dinitrocresol, 2,4-DNOC), in aqueous media are reported. In the probes, the introduction of surface-active hydrophilic "heads" at the periphery of lipophilic (i.e., hydrophobic) pyrene "tails" resulted in the formation of highly fluorescent micelle-like aggregates/pre-associates in aqueous solutions at concentrations of ≤10(-5) m. The enhanced fluorescence quenching of the herein reported architectures is achieved in the presence of ultra-trace amounts of TNT or 2,4-DNT with values of Stern-Volmer quenching constant close to 1×10(5) m(-1) and a detection limit as low as 182 ppb. The most hydrophilic probes demonstrated higher response to 2,4-DNT over TNT. Filter paper test strips impregnated with 1×10(-5) m solutions of the probes were able to detect TNT, 2,4-DNT, and other NACs at levels as low as 50 ppb in water.

Tablet mechanics depend on nano and micro scale adhesion, lubrication and structure

Tablets are the most convenient form for drug administration. However, despite the ease of manufacturing problems such as powder adhesion occur during the production process. This study presents surface and structural characterization of tablets formulated with commonly used excipients (microcrystalline cellulose (MCC), lactose, mannitol, magnesium (Mg) stearate) pressed under different compaction conditions. Tablet surface analyses were performed with scanning electron microscopy (SEM), profilometry and atomic force microscopy (AFM). The mechanical properties of the tablets were evaluated with a tablet hardness test. Local adhesion detected by AFM decreased when Mg stearate was present in the formulation. Moreover, the tablet strength of plastically deformable excipients such as MCC was significantly decreased after addition of Mg stearate. Combined these facts indicate that Mg stearate affects the particle–particle bonding and thus elastic recovery. The MCC excipient also displayed the highest hardness which is characteristic for a highly cohesive material. This is discussed in the view of the relatively high adhesion found between MCC and a hydrophilic probe at the nanoscale using AFM. In contrast, the tablet strength of brittle materials like lactose and mannitol is unaffected by Mg stearate. Thus fracture occurs within the excipient particles and not at particle boundaries, creating new surfaces not previously exposed to Mg stearate. Such uncoated surfaces may well promote adhesive interactions with tools during manufacture.