PEG Size Research Articles

Adsorption characteristics and mechanisms of water-soluble polymers (PVP and PEG) on kaolin and montmorillonite minerals

The excessive use and accumulation of water-soluble polymers (WSPs, known as “liquid plastics”) in the environment can pose potential risks to both ecosystems and human health, but the environmental fate of WSPs remains unclear. Here, the adsorption behavior of WSPs with different molecular weight on kaolinite (Kaol) and montmorillonite (Mt) were examined. The results showed that the adsorption of PEG and PVP on minerals were controlled by hydrogen bond and van der Waals force. The Fourier transform infrared (FTIR) spectra and two-dimensional correlation spectroscopy (2D-COS) analysis revealed that there were interactions between the Al-O and Si-O groups of the minerals and the polar O- or N-containing functional groups as well as the alkyl groups of PEG and PVP. The adsorption characteristics of WSPs were closely related to their molecular weight and the pore size of minerals. Due to the relatively large mesopore size of Kaol, both PEG and PVP were absorbed into inner spaces, for which the adsorption capacity increased with molecular weight of the polymers. For Mt, all types of PEG could enter its micropores, while PVP with larger molecular weights appeared to be confined externally, leading to a decrease in the adsorption capacity of PVP with increasing molecular weight. The findings of this study provide a theoretical basis for scientific evaluation of environmental processes of WSPs.

Effect of Composition and Size on Surface Properties of Anti-Cancer Nanoparticles.

Liposomal formulations offer significant advantages as anticancer drug carriers for targeted drug delivery; however, due to their complexity, clinical translation has been challenging. In addition, liposomal product manufacturing has been interrupted in the past, as was the case for Doxil® (doxorubicin hydrochloride liposome injection). Here, interfacial tension (IFT) measurements were investigated as a potential physicochemical characterization tool to aid in liposomal product characterization during development and manufacturing. A pendant drop method using an optical tensiometer was used to measure the interfacial tension of various analogues of Doxil® liposomal suspensions in air and in dodecane. The effect of liposome concentration, formulation (PEG and cholesterol content), presence of encapsulated drug, as well as average particle size was analyzed. It was observed that Doxil® analog liposomes demonstrate surfactant-like behavior with a sigmoidal-shape interfacial tension vs. concentration curve. This behavior was heavily dependent on PEG content, with a complete loss of surfactant-like behavior when PEG was removed from the formulation. In addition to interfacial tension, three data analyses were identified as able to distinguish between formulations with variations in PEG, cholesterol, and particle size: (i) polar and non-polar contribution to interfacial tension, (ii) liposomal concentration at which the polar and non-polar components were equal, and (iii) rate of interfacial tension decay after droplet formation, which is indicative of how quickly liposomes migrate from the bulk of the solution to the surface. We demonstrate for the first time that interfacial tension can be used to detect certain liposomal formulation changes, such as PEG content, encapsulated drug presence, and size variability, and may make a useful addition to physicochemical characterization during development and manufacturing of liposomal products.

Structure and thermal behaviour of different concentration PEG loaded PVA nanofibers

Poly vinyl alcohol (PVA) has established its credibility in the fields of filtration, biomedical and pharmaceutical areas. In this paper different concentration of poly (ethylene) glycol were added to PVA to prepare gel and its nano fibres. PEG is water soluble similar to PVA can give a uniform gel and a strong intermolecular bonding can be achieved by the addition of PEG in PVA. Fibres were prepared by having high wt.% of PEG loaded PVA nano fibres. Nano fibre mat having 0, 0.2,0.4 and 0.6 g PEG having low molecular weight was added in the 8.6 wt.% PVA solution and then fibres were prepared by using electro spinning technique. Nano fibres so prepared were characterised by SEM, XRD and DSC. SEM results reveal that increase of PEG concentration separated the nano fibres and increased the gap of the mesh size. SEM micro graphs depicts that produced nano fibres are homogenous in nature and there were no apparent gap between the PVA and PEG nano fibre. It may be explained that due to the high electric potential developed during the electro spinning process which helped the nano fibres to get stretched XRD patterns exhibited the crystal size increased on adding PEG in the PVA gel. Effect of PEG addition on Tm of PVA nano fibres has been determined by running their DSC scans. An additional peak of 158.13°C is observed for the sample having 0.4 g PEG. Melting temperature shifted from 215° C to 219°C due to increase in crystal size of PEG added PVA nano fibres.

Polyethylene glycol dictates the therapeutic response (anticancer and wound healing) of silver oxide nanomaterials

AbstractIn this study, polymer (polyethylene glycol [PEG] and Chitosan)‐coated silver oxide nanoparticles (NPs) have been prepared by hydrothermal method. The polymer‐encapsulated NPs are characterized by materials‐related characterization techniques such as X‐Ray diffraction (XRD), scanning electron microscope (SEM), Ultraviolet–visible (UV–Vis), photoluminescence (PL), and Fourier‐transform infrared (FTIR) spectroscopy. The crystallite size of silver oxide NPs is 43.39 nm and reduces to 34.56 nm and 30.43 nm for PEG and Chitosan functionalized NPs, respectively. SEM micrographs show the spherical morphology of the synthesized nanomaterials with the grain size of pristine, PEG, and Chitosan functionalized silver oxide NPs as 60.9 ± 14.1, 70.9 ± 10.3, and 57.2 ± 7.8 nm, respectively. The band gap of silver oxide NPs increases upon polymer functionalization. PEGlyation of silver oxide NPs has enhanced its anticancer potential significantly against liver cancer cell line (HuH‐7), shows least cell viability, and IC50 value is as low as 0.106 μg/mL and in the case of Chitosan coating 4.505 μg/mL. The antibacterial properties and biofilm inhibition are investigated against bacterial extracts of Escherichia coli and Staphylococcus aureus. The polymer‐coated silver oxide NPs have shown enhanced antibacterial potential against both S. aureus and E. coli. CAM assay is used to evaluate the wound‐healing ability of nanomaterials. Alginate gels incorporated with NPs have promoted wound healing. Our results revealed that the surface modification by PEG and Chitosan improved the therapeutic potential of silver oxide NPs.

Mono-PEGylated lysozyme purification with increased productivity and isomer differentiation through heparin monolith chromatography

PEGylated protein purification with the required quality attributes has represented a bioengineering challenge and Affinity Monolith Chromatography (AMC) has never been exploited for this goal. This work reports the generation of a heparin-modified affinity monolith disk by reductive alkylation with raised ligand density for its use as chromatographic support in the separation of lysozyme PEGylation reactions (LPRs) with three different PEG sizes (1, 20 and 40 kDa). For immobilized heparin determination a modified toluidine colorimetric assay adapted to microplate format was proposed. The heparin modified-disk was able to differentiate positional isomers of 20 kDa mono-PEGylated lysozyme at neutral pH using a salt linear gradient. Identity of PEG-conjugates was verified by SDS-PAGE and positional isomers were partially characterized by peptide mapping mass spectrometry. 20 kDa mono-PEGylated lysozyme conjugate purity (99.69 ± 0.05%) was comparable with traditional chromatographic methods while productivity (0.0964 ± 0.0001 mg/mL*min) was increased up to 6.1 times compared to that obtained in heparin packed-bed affinity chromatography procedures. The proposed AMC method represents a reliable, efficient, easy-handling, fast and single-step operation for the analysis or preparative isolation of PEGylated proteins containing a heparin binding domain.

Size-Dependent Interplay of Volume Exclusion Versus Soft Interactions: Cytochrome c in Macromolecular Crowded Environment.

Even though there are a great number of possible conformational states, how a protein generated as a linear unfolded polypeptide efficiently folds into its physiologically active form remained a fascinating and unanswered enigma inside crowded conditions of cells. In this study, various spectroscopic techniques have been exploited to know and understand the effect and mechanism of action of two different sizes of polyethylene glycols, or PEGs (molecular mass ∼10 and ∼20kilo Daltons, kDa), on cytochrome c (cyt c). The outcomes showed that small size of the PEG leads to perturbation of the protein structure, and conversely, large size of the PEG has stabilizing effect on cyt c. Moreover, binding measurements showed that small size of PEG interacts strongly via soft interactions compared to the larger size of PEG, the latter being governed more by excluded volume effect or preferential exclusion from the protein. Overall, this finding suggests that conformations of protein may be influenced in cellular crowded conditions via interactions which depend upon the size of molecule in the environment. This study proposes that both volume exclusion and soft (chemical) interactions governs the protein's conformation and functional activities. The cellular environment's internal architecture as evident from crowder size and shape in this study has a significant role.

Predictive high-throughput screening of PEGylated lipids in oligonucleotide-loaded lipid nanoparticles for neuronal gene silencing.

Lipid nanoparticles (LNPs) are gaining traction in the field of nucleic acid delivery following the success of two mRNA vaccines against COVID-19. As one of the constituent lipids on LNP surfaces, PEGylated lipids (PEG-lipids) play an important role in defining LNP physicochemical properties and biological interactions. Previous studies indicate that LNP performance is modulated by tuning PEG-lipid parameters including PEG size and architecture, carbon tail type and length, as well as the PEG-lipid molar ratio in LNPs. Owing to these numerous degrees of freedom, a high-throughput approach is necessary to fully understand LNP behavioral trends over a broad range of PEG-lipid variables. To this end, we report a low-volume, automated, high-throughput screening (HTS) workflow for the preparation, characterization, and in vitro assessment of LNPs loaded with a therapeutic antisense oligonucleotide (ASO). A library of 54 ASO-LNP formulations with distinct PEG-lipid compositions was prepared using a liquid handling robot and assessed for their physiochemical properties as well as gene silencing efficacy in murine cortical neurons. Our results show that the molar ratio of anionic PEG-lipid in LNPs regulates particle size and PEG-lipid carbon tail length controls ASO-LNP gene silencing activity. ASO-LNPs formulated using PEG-lipids with optimal carbon tail lengths achieved up to 5-fold lower mRNA expression in neurons as compared to naked ASO. Representative ASO-LNP formulations were further characterized using dose–response curves and small-angle X-ray scattering to understand structure–activity relationships. Identified hits were also tested for efficacy in primary murine microglia and were scaled-up using a microfluidic formulation technique, demonstrating a smooth translation of ASO-LNP properties and in vitro efficacy. The reported HTS workflow can be used to screen additional multivariate parameters of LNPs with significant time and material savings, therefore guiding the selection and scale-up of optimal formulations for nucleic acid delivery to a variety of cellular targets.

Characterization of different intermediate states in myoglobin induced by polyethylene glycol: A process of spontaneous molecular self-organization foresees the energy landscape theory via in vitro and in silico approaches

Practically proteins perform their functions exposed to various molecules (macro/micro) of different shapes, sizes, and high concentrations. In such conditions, proteins fold through various intermediate states to execute their type of functions. There are various in vitro studies that showed that proteins yield intermediate states (either pre-molten globule, PMG or molten globules, MG) in changing environments (pH, temperature, and co-solute). Here, we investigate that myoglobin (Mb) yields two intermediate states in the presence of polyethylene glycol, PEG (4 kDa molecular weight) at two different concentrations. These intermediates were characterized by various spectroscopic techniques, further; we demonstrated that these changes in the structure of the protein were due to soft interactions which were confirmed by isothermal titration calorimetric and computational studies. Besides, in silico (molecular dynamic simulations) studies were exploited to know the atomic-level details of the protein which are useful to comprehend the functional characteristics of the bio-molecule with structural change and to study atomic motions and inter-atomic interactions in the bio-molecular systems. This is the first time that two intermediates (MG and PMG state) in the protein (Mb) at two different concentrations in the presence of solo size of PEG are yielded. This study shows folding of a protein does not follow a singular and specific pathway but occurs through routes down a folding funnel more like rain flowing down a funnel, hence foresees the energy landscape theory. Moreover, the study provides the significance of crowding concentrations in the cellular organism.

Anti-Cancer Activities of Thyrointegrin αvβ3 Antagonist Mono- and Bis-Triazole Tetraiodothyroacetic Acid Conjugated via Polyethylene Glycols in Glioblastoma.

Simple SummaryDifferent Triazole Tetrac (TAT) thyrointegrin αvβ3 antagonists exhibited optimal therapeutic efficacy against U87 or primary glioblastoma cells. TAT containing molecules bind with high affinity to the integrin αvβ3 and plasma protein Transthyretin (TTR), which facilitate transport across the blood brain barrier. Biological studies showed that decreasing the PEG linker size (1600 versus 4000) or having mono-TAT versus bi-TAT had no significant impact on their αvβ3 binding affinity, anti-angiogenesis, and overall anti-cancer efficacy.Integrin αvβ3 receptors are overexpressed in different tumors and their associated neovascularization and hence, represent a potential cancer target. We previously synthesized a high affinity thyrointegrin αvβ3, P4000-bi-TAT (tetrac derivative), with potent anticancer properties. However, the long polydisperse PEG conjugate showed large scaleup and analytical/bioanalytical issues. Hence, in the present study, we synthesized a mono versus bi-triazole tetrac with discrete monodisperse PEG, which provided improvement in scaleup and bioanalysis. In the present study, we compared binding affinity and anticancer activates with a smaller PEG size (P1600-bi-TAT, Compound 2) and the removal of one TAT molecule (P1600-m-TAT, Compound 3) versus P4000-bi-TAT, Compound 1. The results of the selectivity and affinity of TATs showed greater affinity to integrin αvβ3. The xenograft weights and tumor cell viabilities were decreased by >90% at all doses compared to the control (ON Treatment, *** p < 0.001) in cells treated with Compounds 1, 2, and 3 in U87-Luc-treated mice. The in vivo luminescent signals of U87-luc cells reflect the proliferation and distribution of tumor cells in the animals and the maximum intensity corresponding to the maximum tumor cells that the animals could tolerate. We found that the three thyrointegrin αvβ3 antagonists exhibited optimal therapeutic efficacy against U87 or primary glioblastoma cells. Biological studies showed that decreasing the PEG linker size (1600 vs. 4000) or having mono-TAT or bi-TAT had no significant impact on their αvβ3 binding affinity, anti-angiogenesis, or overall anti-cancer efficacy.

Synthesis of Poly(ether‐ester‐urethane) with a Controlled Molar Mass Based on Poly(ε‐caprolactone) and Poly(ethylene glycol) Segments

AbstractPoly(ether‐ester‐urethanes) (PEEUs) derived from poly(ε‐caprolactone) and poly(ethylene glycol) (PCL‐b‐PEG) have a high potential for use in biomedical applications or as compatibilizers of immiscible poly(acid lactic) and poly(ε‐caprolactone) (PLA/PCL) blends. This study focused on the synthesis of PEEUs with same molar mass by one‐step bulk polycondensation of PCL and PEG macrodiols and hexamethylene diisocyanate (HDI). The copolymers, distinguished by the size of hydrophilic PEG and hydrophobic PCL segments and symmetry of the blocks, are characterized by SEC, FTIR, H1‐NMR, TGA, DSC, and water absorption testing. FTIR and H1‐NMR results demonstrated the formation of a hydroxy‐terminated multiblock copolymer with urethane bonds. Additionally, the PEG:PCL compositions measured by H1‐NMR are close to the theoretical compositions. Molar mass distribution curves revealed that copolymers with molar mass around 45 000 Da are synthesized by varying extents of ratio, given by NCO/OH molar ratio, between 0.9 and 1.0 depending on the initial macrodiols molar masses. The block size ratio of hydrophilic and hydrophobic blocks is an important parameter in water absorption behavior, which can generate a water‐uptake of 50% or even 350% depending on the symmetry of the segments.

Optimization of Liposomes for Antigen Targeting to Splenic CD169+ Macrophages.

Despite promising progress in cancer vaccination, therapeutic effectiveness is often insufficient. Cancer vaccine effectiveness could be enhanced by targeting vaccine antigens to antigen-presenting cells, thereby increasing T-cell activation. CD169-expressing splenic macrophages efficiently capture particulate antigens from the blood and transfer these antigens to dendritic cells for the activation of CD8+ T cells. In this study, we incorporated a physiological ligand for CD169, the ganglioside GM3, into liposomes to enhance liposome uptake by CD169+ macrophages. We assessed how variation in the amount of GM3, surface-attached PEG and liposomal size affected the binding to, and uptake by, CD169+ macrophages in vitro and in vivo. As a proof of concept, we prepared GM3-targeted liposomes containing a long synthetic ovalbumin peptide and tested the capacity of these liposomes to induce CD8+ and CD4+ T-cell responses compared to control liposomes or soluble peptide. The data indicate that the delivery of liposomes to splenic CD169+ macrophages can be optimized by the selection of liposomal constituents and liposomal size. Moreover, optimized GM3-mediated liposomal targeting to CD169+ macrophages induces potent immune responses and therefore presents as an interesting delivery strategy for cancer vaccination.

A supramolecular platform for controlling and optimizing molecular architectures of siRNA targeted delivery vehicles.

It requires multistep synthesis and conjugation processes to incorporate multifunctionalities into a polyplex gene vehicle to overcome numerous hurdles during gene delivery. Here, we describe a supramolecular platform to precisely control, screen, and optimize molecular architectures of siRNA targeted delivery vehicles, which is based on rationally designed host-guest complexation between a β-cyclodextrin-based cationic host polymer and a library of guest polymers with various PEG shape and size, and various density of ligands. The host polymer is responsible to load/unload siRNA, while the guest polymer is responsible to shield the vehicles from nonspecific cellular uptake, to prolong their circulation time, and to target tumor cells. A series of precisely controlled molecular architectures through a simple assembly process allow for a rapid optimization of siRNA delivery vehicles in vitro and in vivo for therapeutic siRNA-Bcl2 delivery and tumor therapy, indicating the platform is a powerful screening tool for targeted gene delivery vehicles.

Effect of plasticiser on the morphology, mechanical properties and permeability of albumen-based nanobiocomposites

Abstract This paper delves into the role plasticisers play in the formulation and processing of bioplastics and nanobiocomposites, trying to understand their effect on nanoclays dispersion and, consequently, on mechanical and gas barrier properties of protein-based nanobiocomposites. Egg white protein/montmorillonite clay nanobiocomposites were obtained by thermomechanical processing plasticised with varying molar concentration of different components (water, glycerol, polyethylene glycol). The extent of dispersion of the filler was evaluated by X-ray diffraction and transmission electron microscopy. Tensile tests and solid-state rheological measurements were conducted to evaluate glass transition temperature and thermomechanical behaviour of plasticised protein-clay nanobiocomposites, whereas gas permeability tests were used to study their gas barrier properties. The results showed that the samples plasticised by a blend of 1:1 glycerol/water presented the most exfoliated structures, resulting in an improvement in gas barrier and mechanical properties. Morphological analyses combined with tensile and permeability tests have shown a lesser effect of polyethylene glycol of 300 molecular weight (PEG 300) on the exfoliation extent into such nanobiocomposites. Moreover, the larger size of PEG 300 does not allow the formation of a structure as compact as in the case of water and glycerol, as a consequence of an apparent phase separation, leaving more spaces that facilitate the diffusion of gases through the material.

Spalling resistance of thermally grown oxide based on NiCoCrAlY(Ti) with different oxide peg sizes

NiCoCrAlY is usually used as the material to bond-coat in thermal barrier coating systems under high temperatures. Using NiCoCrAlY and adding different amounts of the active element Ti (0, 0.1, 0.3, and 0.5; wt%), the relationship between oxide peg size and thermally grown oxide spalling resistance is ascertained by examining specimens subjected to a cyclic oxidation experiment. Oxide pegs, consisting of a Y- and Ti-rich oxide core and an outer Al2O3 sheath, are formed by Ti and Al successively reacting with oxygen after the rapid generation of Y-rich oxide. The size of the oxide pegs with higher Ti concentrations is on average bigger in the alloy. Severe thermally grown oxide spalling occurred in the 0.5 wt% Ti specimen, but in the 0.3 wt% Ti specimen, it displayed the best adherence with the alloy due to the presence of fine pegs. Cavities existed at the interface between the inner oxide core and outer Al2O3 sheath of larger pegs serve as microcrack sources and further induce severe scale failure combined with the initial interface crack between the scale and alloy.

Insights into the Folding Pathway of a c-MYC-Promoter-Based i-Motif DNA in Crowded Environments at the Single-Molecule Level.

Cytosine-rich DNA sequences fold into secondary structures called i-Motifs, which are usually stable at acidic pH. However, molecular crowding agents, such as poly(ethylene glycol) (PEG), are known to facilitate the formation of these structures even at neutral pH. As crowding mimics the intracellular environment and not much is known about the folding pathway of i-Motifs in such constrained media, we have probed, in detail, the conformational changes of a 22-mer c-MYC-promoter-based C-rich sequence (Py22) in the presence of PEG, employing Förster resonance energy transfer and fluorescence lifetime measurements at the single-molecule level. We find that the folding process is not a simple two-state transition between a random coil and a folded i-Motif structure. Rather, it involves a partially folded conformation as an intermediate in which the bases are not as efficiently stacked as in the completely folded i-Motif form. The relative population of each species is governed by the size and concentration of PEG, and 30% (w/w) PEG6000 is the optimum condition for the folding of Py22. Under this condition, ∼80% of Py22 exists in the fully folded i-Motif form and ∼20% of it is in the partially folded state.

Structural basis of polyethylene glycol recognition by antibody

BackgroundPolyethylene glycol (PEG) is widely used in industry and medicine. Anti-PEG antibodies have been developed for characterizing PEGylated drugs and other applications. However, the underlying mechanism for specific PEG binding has not been elucidated.MethodsThe Fab of two cognate anti-PEG antibodies 3.3 and 2B5 were each crystallized in complex with PEG, and their structures were determined by X-ray diffraction. The PEG-Fab interactions in these two crystals were analyzed and compared with those in a PEG-containing crystal of an unrelated anti-hemagglutinin 32D6-Fab. The PEG-binding stoichiometry was examined by using analytical ultracentrifuge (AUC).ResultsA common PEG-binding mode to 3.3 and 2B5 is seen with an S-shaped core PEG fragment bound to two dyad-related Fab molecules. A nearby satellite binding site may accommodate parts of a longer PEG molecule. The core PEG fragment mainly interacts with the heavy-chain residues D31, W33, L102, Y103 and Y104, making extensive contacts with the aromatic side chains. At the center of each half-circle of the S-shaped PEG, a water molecule makes alternating hydrogen bonds to the ether oxygen atoms, in a similar configuration to that of a crown ether-bound lysine. Each satellite fragment is clamped between two arginine residues, R52 from the heavy chain and R29 from the light chain, and also interacts with several aromatic side chains. In contrast, the non-specifically bound PEG fragments in the 32D6-Fab crystal are located in the elbow region or at lattice contacts. The AUC data suggest that 3.3-Fab exists as a monomer in PEG-free solution but forms a dimer in the presence of PEG-550-MME, which is about the size of the S-shaped core PEG fragment.ConclusionsThe differing amino acids in 3.3 and 2B5 are not involved in PEG binding but engaged in dimer formation. In particular, the light-chain residue K53 of 2B5-Fab makes significant contacts with the other Fab in a dimer, whereas the corresponding N53 of 3.3-Fab does not. This difference in the protein-protein interaction between two Fab molecules in a dimer may explain the temperature dependence of 2B5 in PEG binding, as well as its inhibition by crown ether.

Tumor-triggered personalized microRNA cocktail therapy for hepatocellular carcinoma.

As one of the most malignant primary cancers, hepatocellular carcinoma (HCC) still lacks an efficient therapeutic strategy to date. Here, we developed a polymer-based nanoplatform PEI-βCD@Ad-CDM-PEG (PCACP) for functional microRNA (miRNA) therapy. PCACP exhibits excellent stability in physiological solutions, but sensitive PEG detachment and size transformation in an acidic tumor environment due to the breakdown of pH-responsive linkages, promoting tumor penetration and cellular uptake of nanoparticles, further facilitating transfection efficiency due to the proton sponge effect of polycations. We present a novel miRNA cocktail therapy by encapsulating miR-199a/b-3p mimics (miR199) and antimiR-10b (antimiR10b) into PCACP for eliminating HCC. Validated by qRT-PCR, immunoblotting and immunohistochemistry, compared with miR199 or antimiR10b delivered alone, miR-cocktail therapy substantially inhibits HCC cell proliferation and tumor growth by targeting mTOR, PAK4, RHOC and epithelial-mesenchymal transition (EMT) pathways both in vitro and in vivo (i.v. injection). Furthermore, we proposed personalized miR-cocktail therapy by adjusting the encapsulated miRNA formula according to the miRNA profiling of a patient's tumor sample. The personalized PCACP/miR-cocktail system exhibits significant tumor suppression and multitarget regulation on patient derived xenografts (PDXs), representing a notable effect improvement over conventional gene therapy. The tumor-acidity-cleavable PCACP/miR-cocktail system, with loaded miRNA controllability and high transfection efficiency, is a promising personalized therapeutic strategy for future HCC treatment.

Quantitatively Fine-Tuning the Physicochemical and Biological Properties of Peptidic Polymers through Monodisperse PEGylation.

In biomedicine, PEGylation is one of the most successful strategies to modify the physicochemical and biological properties of peptides, proteins, and other biomacromolecules. Because of the polydisperse nature of regular PEGs and limited PEGylation strategies, it is challenging to quantitatively fine-tune and accurately predict the properties of biomacromolecules after PEGylation. However, such fine-tuning and prediction may be crucial for their biomedical applications. Herein, some monodisperse PEGylation strategies, including backbone PEGylation, side-chain PEGylation, and highly branched PEGylation, have been developed. In a comparative fashion, the impact of PEGylation strategies and monodisperse PEG sizes on the physicochemical and biological properties, including lipophilicity, thermosensitivity, biocompatibility, plasma stability, and drug delivery capability, of peptidic polymers has been quantitatively studied. It was found that the physicochemical and biological properties of PEGylated peptidic polymers can be quantitatively fine-tuned and accurately predicted through these monodisperse PEGylation strategies. After the comparative study, a side-chain monodisperse PEGylated peptidic polymer was chosen as fluorine-19 magnetic resonance and fluorescence dual-imaging traceable drug delivery vehicle. Our study may not only promote the transformation of PEGylation from an empirical technology to a quantitative science but also shed light on the rational design of PEGylated biomaterials and pharmaceutics.

Analytical Model To Describe the Effect of Polyethylene Glycol on Ionic Screening of Analyte Charges in Transistor-Based Immunosensing.

Recently, the co-immobilization of polyethylene glycol has improved sensor responses of transistor-based immunosensing by approximately three times. However, there is currently no analytical model available to explain this empirical effect. The key parameters thought to affect the potential are the receptor density, the capacitance, the analyte charge, and the dissociation constant. Based on our experimental data, only the analyte charge can account for the signal enhancement. To capture the effect of PEG on the analyte charge, we introduce a prefactor, the detectable charge qdet, which represents the portion of analyte charges effectively detected by the sensor. This parameter can quantitatively describe the PEG-induced signal enhancement and can be used to recommend the choice of PEG size for immuno-field-effect transistors. Additionally, we include the competition between electrolyte ions and the analyte for binding to the recognition molecule to more accurately describe the concentration-dependent sensor responses than the traditional Langmuir binding model does.

Reversible Control of Spacing in Charged Lamellar Membrane Hydrogels by Hydrophobically Mediated Tethering with Symmetric and Asymmetric Double-End-Anchored Poly(ethylene glycol)s.

Complex materials often achieve their remarkable functional properties by hierarchical assembly of building blocks via competing and/or synergistic interactions. Here, we describe the properties of new double-end-anchored poly(ethylene glycol)s (DEA-PEGs)-macromolecules designed to impart hydrophobically mediated tethering attractions between charged lipid membranes. We synthesized DEA-PEGs (MW 2000 (2K) and 4.6K) with two double-tail (symmetric) or a double-tail and a single-tail (asymmetric) hydrophobic end anchors and characterized their equilibrium and kinetic properties using small-angle X-ray scattering. Control multilayer membranes without and with PEG lipid (i.e., single-end-anchored PEG) swelled continuously, with the interlayer spacing increasing between 30 and 90 wt % water content due to electrostatic as well as, in the case of PEG lipid, steric repulsion. In contrast, interlayer spacings in lamellar membrane hydrogels containing DEA-PEGs expanded over a limited water dilution range and reached a "locked" state, which displayed a near constant membrane wall-to-wall spacing (δw) with further increases in water content. Remarkably, the locked state displays a simple relation to the PEG radius of gyration δw ≈ 1.6 RG for both 2K and 4.6K PEG. Nevertheless, δw being considerably less than the physical size of PEG (2(5/3)1/2 RG) is highly unexpected and implies that, compared to free PEG, anchoring of the PEG tether at both ends leads to a considerable distortion of the PEG conformation confined between layers. Significantly, the lamellar hydrogel may be designed to reversibly transition from a locked to an unlocked (membrane unbinding) state by variations in the DEA-PEG concentration, controlling the strength of the interlayer attractions due to bridging conformations. The findings with DEA-PEGs have broad implications for hydrophobic-mediated assembly of lipid- or surfactant-coated building blocks with distinct shape and size, at predictable spacing, in aqueous environments.