Reflections on a Copenhagen-Minneapolis Axis in Bioorganic Chemistry.

The international peptide community rejoiced when one of its most distinguished members, Morten Meldal of Denmark, shared the 2022 Nobel Prize in Chemistry. In fact, the regiospecific solid-phase "copper(I)-catalyzed 1,3-dipolar cycloaddition of terminal alkynes to azides" (CuACC) reaction-that formed the specific basis for Meldal's recognition-was reported first at the 17th American Peptide Symposium held in San Diego in June 2001. The present perspective outlines intertwining conceptual and experimental threads pursued concurrently in Copenhagen and Minneapolis, sometimes by the same individuals, that provided context for Meldal's breakthrough discovery. Major topics covered include orthogonality in chemistry; the dithiasuccinoyl (Dts) protecting group for amino groups in α-amino acids, carbohydrates, and monomers for peptide nucleic acids (PNA); and poly(ethylene glycol) (PEG)-based solid supports such as PEG-PS, PEGA, and CLEAR [and variations inspired by them] for solid-phase peptide synthesis (SPPS), solid-phase organic synthesis (SPOS), and combinatorial chemistry that can support biological assays in aqueous media.

Enhancing protein dynamics analysis with hydrophilic polyethylene glycol cross-linkers.

Cross-linkers play a critical role in capturing protein dynamics in chemical cross-linking mass spectrometry techniques. Various types of cross-linkers with different backbone features are widely used in the study of proteins. However, it is still not clear how the cross-linkers' backbone affect their own structure and their interactions with proteins. In this study, we systematically characterized and compared methylene backbone and polyethylene glycol (PEG) backbone cross-linkers in terms of capturing protein structure and dynamics. The results indicate the cross-linker with PEG backbone have a better ability to capture the inter-domain dynamics of calmodulin, adenylate kinase, maltodextrin binding protein and dual-specificity protein phosphatase. We further conducted quantum chemical calculations and all-atom molecular dynamics simulations to analyze thermodynamic and kinetic properties of PEG backbone and methylene backbone cross-linkers. Solution nuclear magnetic resonance was employed to validate the interaction interface between proteins and cross-linkers. Our findings suggest that the polarity distribution of PEG backbone enhances the accessibility of the cross-linker to the protein surface, facilitating the capture of sites located in dynamic regions. By comprehensively benchmarking with disuccinimidyl suberate (DSS)/bis-sulfosuccinimidyl-suberate(BS3), bis-succinimidyl-(PEG)2 revealed superior advantages in protein dynamic conformation analysis in vitro and in vivo, enabling the capture of a greater number of cross-linking sites and better modeling of protein dynamics. Furthermore, our study provides valuable guidance for the development and application of PEG backbone cross-linkers.

Impact of Anti-PEG IgM Induced via the Topical Application of a Cosmetic Product Containing PEG Derivatives on the Antitumor Effects of PEGylated Liposomal Antitumor Drug Formulations in Mice.

Poly(ethylene glycol) (PEG) is used in many common products, such as cosmetics. PEG, however, is also used to covalently conjugate drug molecules, proteins, or nanocarriers, which is termed PEGylation, to serve as a shield against the natural immune system of the human body. Repeated administration of some PEGylated products, however, is known to induce anti-PEG antibodies. In addition, preexisting anti-PEG antibodies are now being detected in healthy individuals who have never received PEGylated therapeutics. Both treatment-induced and preexisting anti-PEG antibodies alter the pharmacokinetic properties, which can result in a subsequent reduction in the therapeutic efficacy of administered PEGylated therapeutics through the so-called accelerated blood clearance (ABC) phenomenon. Moreover, these anti-PEG antibodies are widely reported to be related to severe hypersensitivity reactions following the administration of PEGylated therapeutics, including COVID-19 vaccines. We recently reported that the topical application of a cosmetic product containing PEG derivatives induced anti-PEG immunoglobulin M (IgM) in a mouse model. Our finding indicates that the PEG derivatives in cosmetic products could be a major cause of the preexistence of anti-PEG antibodies in healthy individuals. In this study, therefore, the pharmacokinetics and therapeutic effects of Doxil (doxorubicin hydrochloride-loaded PEGylated liposomes) and oxaliplatin-loaded PEGylated liposomes (Liposomal l-OHP) were studied in mice. The anti-PEG IgM antibodies induced by the topical application of cosmetic products obviously accelerated the blood clearance of both PEGylated liposomal formulations. Moreover, in C26 tumor-bearing mice, the tumor growth suppressive effects of both Doxil and Liposomal l-OHP were significantly attenuated in the presence of anti-PEG IgM antibodies induced by the topical application of cosmetic products. These results confirm that the topical application of a cosmetic product containing PEG derivatives could produce preexisting anti-PEG antibodies that then affect the therapeutic efficacy of subsequent doses of PEGylated therapeutics.

Structurally decoupled stiffness and solute transport in multi-arm poly(ethylene glycol) hydrogels.

Synthetic hydrogels are widely used as artificial 3D environments for cell culture, facilitating the controlled study of cell-environment interactions. However, most hydrogels are limited in their ability to represent the physical properties of biological tissues because stiffness and solute transport properties in hydrogels are closely correlated. Resultingly, experimental investigations of cell-environment interactions in hydrogels are confounded by simultaneous changes in multiple physical properties. Here, we overcame this limitation by simultaneously manipulating four structural parameters to synthesize a library of multi-arm poly (ethylene glycol) (PEG) hydrogel formulations with robustly decoupled stiffness and solute transport. This structural design approach avoids chemical alterations or additions to the network that might have unanticipated effects on encapsulated cells. An algorithm created to statistically evaluate stiffness-transport decoupling within the dataset identified 46 of the 73 synthesized formulations as robustly decoupled. We show that the swollen polymer network model accurately predicts 11 out of 12 structure-property relationships, suggesting that this approach to decoupling stiffness and solute transport in hydrogels is fundamentally validated and potentially broadly applicable. Furthermore, the unprecedented control of hydrogel network structure provided by multi-arm PEG hydrogels confirmed several fundamental modeling assumptions. This study enables nuanced hydrogel design for uncompromised investigation of cell-environment interactions.

Tissue-Adhesive Hydrogel Spray System for Live Cell Immobilization on Biological Surfaces.

Gelatin hydrogels are used as three-dimensional cell scaffolds and can be prepared using various methods. One widely accepted approach involves crosslinking gelatin amino groups with poly(ethylene glycol) (PEG) modified with N-hydroxysuccinimide ester (PEG-NHS). This method enables the encapsulation of live cells within the hydrogels and also facilitates the adhesion of the hydrogel to biological tissues by crosslinking their surface amino groups. Consequently, these hydrogels are valuable tools for immobilizing cells that secrete beneficial substances in vivo. However, the application of gelatin hydrogels is limited due to the requirement for several minutes to solidify under conditions of neutral pH and polymer concentrations suitable for live cells. This limitation makes it impractical for use with biological tissues, which have complex shapes or inclined surfaces, restricting its application to semi-closed spaces. In this study, we propose a tissue-adhesive hydrogel that can be sprayed and immobilized with live cells on biological tissue surfaces. This hydrogel system combines two components: (1) gelatin/PEG-NHS hydrogels and (2) instantaneously solidifying PEG hydrogels. The sprayed hydrogel solidified within 5 s after dispensing while maintaining the adhesive properties of the PEG-NHS component. The resulting hydrogels exhibited protein permeability, and the viability of encapsulated human mesenchymal stem/stromal cells (hMSCs) remained above 90% for at least 7 days. This developed hydrogel system represents a promising approach for immobilizing live cells on tissue surfaces with complex shapes.

Simple Preparation of Injectable Hydrogels with Phase-Separated Structures That Can Encapsulate Live Cells.

Injectable hydrogels are biomaterials that can be administered minimally invasively in liquid form and are considered promising artificial extracellular matrix (ECM) materials. However, ordinary injectable hydrogels are synthesized from water-soluble molecules to ensure injectability, resulting in non-phase-separated structures, making them structurally different from natural ECMs with phase-separated insoluble structural proteins, such as collagen and elastin. Here, we propose a simple material design approach to impart phase-separated structures to injectable hydrogels by adding inorganic salts. Injecting a gelling solution of mutually cross-linkable tetra-arm poly(ethylene glycol)s with potassium sulfate at optimal concentrations results in the formation of a hydrogel with phase-separated structures in situ. These phase-separated structures provide up to an 8-fold increase in fracture toughness while allowing the encapsulation of live mouse chondrogenic cells without compromising their proliferative activity. Our findings highlight that the concentration of inorganic salts is an important design parameter in injectable hydrogels for artificial ECMs.

Development of blend PEG-PES/NMP-DMF mixed matrix membrane for CO2/N2 separation.

The carbon dioxide (CO2) separation technology has become a focus recently, and a developed example is the membrane technology. It is an alternative form of enhanced gas separation performance above the Robeson upper bound line resulting in the idea of mixed matrix membranes (MMMs). With attention given to membrane technologies, the MMMs were fabricated to have the most desirable gas separation performance. In this work, blend MMMs were synthesised by using two polymers, namely, poly(ether sulfone) (PES) and poly (ethylene glycol) (PEG). These polymers were dissolved in blend N-methyl-2-pyrrolidone (NMP) and dimethylformamide (DMF) solvents with the functionalised multi-walled carbon nanotubes (MWCNTs-F) fillers by using the mixing solution method. The embedding of the pristine MWCNTs and MWCNTs-F within the new synthesised MMM was then studied towards CO2/N2 separation. In addition, the optimisation of the loading of MWCNTs-F for blend MMM for CO2/N2 separation was also studied. The experimental results showed that the functionalised MWCNTs (MWCNTs-F) were a better choice at enhancing gas separation compared to the pristine MWCNTs (MWCNTs-P). Additionally, the effects of MWCNTs-F at loadings 0.01 to 0.05% were studied along with the polymer compositions for PES:PEG of 10:20, 20:20 and 30:10. Both these parameters of study affect the manner of gas separation performance in the blend MMMs. Overall, the best performing membrane showed a selectivity value of 1.01 + 0.05 for a blend MMM (MMM-0.03F) fabricated with 20 wt% of PES, 20 wt% of PEG and 0.03 wt% of MWCNTs-F. The MMM-0.03F was able to withstand a pressure of 2 bar, illustrating its mechanical strength and ability to be used in the post combustion carbon capture application industries where the flue gas pressure is at 1.01 bar.

To PEGylate or not to PEGylate: Immunological properties of nanomedicine's most popular component, polyethylene glycol and its alternatives.

Polyethylene glycol or PEG has a long history of use in medicine. Many conventional formulations utilize PEG as either an active ingredient or an excipient. PEG found its use in biotechnology therapeutics as a tool to slow down drug clearance and shield protein therapeutics from undesirable immunogenicity. Nanotechnology field applies PEG to create stealth drug carriers with prolonged circulation time and decreased recognition and clearance by the mononuclear phagocyte system (MPS). Most nanomedicines approved for clinical use and experimental nanotherapeutics contain PEG. Among the most recent successful examples are two mRNA-based COVID-19 vaccines that are delivered by PEGylated lipid nanoparticles. The breadth of PEG use in a wide variety of over the counter (OTC) medications as well as in drug products and vaccines stimulated research which uncovered that PEG is not as immunologically inert as it was initially expected. Herein, we review the current understanding of PEG's immunological properties and discuss them in the context of synthesis, biodistribution, safety, efficacy, and characterization of PEGylated nanomedicines. We also review the current knowledge about immunological compatibility of other polymers that are being actively investigated as PEG alternatives.

Control Release Coating for Urinary Catheters with Enhanced Released Profile for Sustained Antimicrobial Protection.

Catheter-associated urinary tract infections (CAUTIs) are common and pose significant costs to healthcare systems. To date, this problem is largely unsolved as commercially available antimicrobial catheters are still lacking in functionality and performance. A prior study by Lim et al. ( Biotechnol. Bioeng. 2018, 115 (8), 2000-2012) reported the development of a novel anhydrous polycaprolactone (PCL) polymer formulation with controlled-release functionality for antimicrobial peptides. In this follow-up study, we developed an improved antimicrobial peptide (AMP)-impregnated poly(ethylene glycol) (PEG)-polycaprolactone (PCL) anhydrous polymer coating for enhanced sustained controlled-release functionality to provide catheters with effective antimicrobial properties. Varying the ratio of PEG and PEG-PCL copolymers resulted in polymers with different morphologies, consequently affecting the AMP release profiles. The optimal coating, formulated with 10% (w/w) PEG-PCL in PCL, achieved a controlled AMP release rate of 31.65 ± 6.85 µg/mL daily for up to 19 days, with a moderate initial burst release. Such profile is desired for antimicrobial coating as the initial burst release acts as a sterilizer to kill the bacteria present in the urinary tract upon insertion, and the subsequent linear release functions as a prophylaxis to deter opportunistic microbial infections. As a proof-of-concept application, our optimized coating was then applied to a commercial silicone catheter for further antibacterial tests. Preliminary results revealed that our coated catheters outperformed commercial silver-based antimicrobial catheters in terms of antimicrobial performance and sustainability, lasting for 4 days. Application of the controlled-release coating also aids in retarding biofilm formation, showing a lower extent of biofilm formation at the end of seven inoculation cycles.

Porous nanoparticles with engineered shells release their drug cargo in cancer cells.

Highly porous nanoscale metal-organic frameworks (nanoMOFs) attract growing interest as drug nanocarriers. However, engineering "stealth" nanoMOFs with poly(ethylene glycol) (PEG) coatings remains a main challenge. Here we address the goal of coating nanoMOFs with biodegradable shells using novel cyclodextrin (CD)-based oligomers with a bulky structure to avoid their penetration inside the open nanoMOF porosity. The PEG chains were grafted by click chemistry onto the CDs which were further crosslinked by citric acid. Advantageously, the oligomers' free citrate units allowed their spontaneous anchoring onto the nanoMOFs by complexation with the iron sites in the top layers. Up to 31 wt% oligomers could be firmly attached by simple incubation with the nanoMOFs in an aqueous medium. Moreover, the anticancer drug doxorubicin (DOX) was successfully entrapped in the core-shell nanoMOFs with loadings up to 41 wt%. High resolution STEM (HR-STEM) showed that the organized crystalline structures were preserved. Remarkably, at the highest loadings, DOX was poorly released out of the nanoMOFs at pH 7.4 (<2% in 2 days). In contrast, around 80% of DOX was released out at pH 4.5 of artificial lysosomal fluid in 24 h. Confocal microscopy investigations showed that the DOX-loaded nanoMOFs penetrated inside Hela cancer cell together with their PEG shells. There, they released the DOX cargo which further diffused inside the nucleus to eradicate the cancer cells.

Towards a better mechanistic comprehension of drug permeation and absorption: Introducing the diffusion-partitioning interplay.

The process of passive drug absorption from the gastrointestinal tract is still poorly understood and modelled. Additionally, the rapidly evolving field of pharmaceutics demands efficient, affordable and reliable in vitro tools for predicting in vivo performance. In this work, we combined established methods for quantifying drug diffusivity (localized UV-spectroscopy) and permeability (Permeapad® plate) in order to gain a better understanding of the role of unstirred water layers (UWLs) in drug absorption. The effect of diffusion/permeability media composition and viscosity on the apparent permeation resistance (Rapp) of model drugs caffeine (CAF) and hydrocortisone (HC) were tested and evaluated by varying the type and concentration of viscosity-enhancing agent - glycerol or a poly(ethylene glycol) (PEG) with different average molecular weights. For all types of media, increased viscosity lead to reduction in diffusivity but could not alone explain the observed effect, which was attributed to intermolecular polymer-drug interactions. Additionally, for both drugs, smaller hydrophilic viscosity-enhancing agents (glycerol and PEG 400) had larger influence than larger ones (PEG 3350 and 6000). The results highlighted the role of UWL as an additive barrier to permeation and indicated that diffusion through UWL is the rate-limiting step to CAF's permeation, whilst HC permeability is a partition-driven process.

Conformation of poly(ethylene glycol) in aqueous cholinium amino acid hybrid solvents.

HYPOTHESIS: Hybrid solvents based on cholinium amino acid ionic liquids ([Ch][AA] ILs) mixed with water are environmentally benign solvents with low toxicity. [Ch][AA] ILs are used in biomass pretreatment processes to dissolve targeted (macro)molecules such as lignin from lingnocellulose. Understanding how [Ch][AA] ILs dissolve polymers is therefore of great interest for the rational design of ILs towards industrial application. Variation of the IL anion and the water concentration are hypothesised to change the solvent properties of [Ch][AA] hybrid solvents. Therefore, we probe the solvent quality of [Ch][AA] aqueous solutions with different anions (glycinate, prolinate and argininate) and water concentration for the simple model solute poly(ethylene glycol) (PEG). EXPERIMENTS: Partial phase diagrams were produced to probe the salting-out effect of [Ch][AA] ILs towards PEG (Mw = 38 kDa). Small-angle neutron scattering experiments of deuterated PEG in hydrogenous [Ch][AA] aqueous solutions were performed to determine the polymer radius of gyration at infinite dilution (Rg,0) via Zimm-plots. Polymer concentration dependent apparent Rg values were obtained fitting an excluded volume polymer model onto the scattering data. Blends of hydrogenous and deuterated PEG under zero average contrast conditions were analysed to probe Rg at high polymer concentrations. FINDINGS: Hydrogen bond capacity of the anion is key to the salting-out effect of [Ch][AA] ILs on PEG. Rg,0 depends on anion species and water concentration. At IL:water = 1:30 (mole:mole) and 37 °C, cholinium argininate and cholinium glycinate are close to theta solvents while cholinium prolinate and dilute cholinium argininate (IL:water = 1:100) are between theta and good solvents.

Understanding near-surface polymer dynamics by a combination of grazing-incidence neutron scattering and virtual experiments.

Neutron spin-echo spectroscopy is a unique experimental method for the investigation of polymer dynamics. The combination of neutron spin-echo spectroscopy with grazing-incidence geometry (GINSES) opens the possibility to probe the dynamics of soft-matter materials in the vicinity of the solid substrate in the time range up to 100 ns. However, the usage of the GINSES technique has some peculiarities and, due to the novelty of the method and complexity of the scattering geometry, difficulties in further data analysis occur. The current work discusses how virtual experiments within the distorted-wave Born approximation using the BornAgain software can improve GINSES data treatment and aid the understanding of polymer dynamics in the vicinity of the solid surface. With two examples, poly(N-isopropyl acrylamide) brushes and poly(ethylene glycol) microgels on Si surfaces, the simulation as well as the application of the simulation to the GINSES data analysis are presented. The approach allowed a deeper insight to be gained of the background effect and scattering contribution of different layers.

PEG/PEI-functionalized single-walled carbon nanotubes as delivery carriers for doxorubicin: synthesis, characterization, and in vitro evaluation.

Single-walled carbon nanotubes (SWCNTs) have attracted great interest regarding drug-delivery applications. However, their application has been limited by some inherent disadvantages. In this study, raw SWCNTs were purified with different oxidizing acids, and the resulting shortened CNTs were conjugated with poly(ethylene glycol) (PEG) and polyethylenimine (PEI). The different nanocarriers, that is, CNTs-COOH (CNTs), CNTs-PEG and CNTs-PEG-PEI, were systematically characterized and evaluated in terms of drug loading, in vitro release, cytotoxicity towards MCF-7 cells and cellular uptake. The results showed that all CNT carriers had a high drug loading capacity. In comparison with CNTs-COOH and CNTs-PEG, CNTs-PEG-PEI showed a more rapid drug release under acidic conditions and a higher antitumor activity. Furthermore, fluorescence detection and flow cytometry (FCM) analysis results indicated that the internalization into cells of CNTs-PEG-PEI was significantly enhanced, thus inducing tumor cell death through apoptosis more efficiently. The above series of benefits of CNTs-PEG-PEI may be attributed to their good dispersibility and comparably higher affinity to tumor cells due to the difunctionalization. In summary, the PEG- and PEI-conjugated CNTs may be used as novel nanocarriers and the findings will contribute to the rational design of multifunctional delivery vehicles for anticancer drugs.

Printability, Mechanical and Thermal Properties of Poly(3-Hydroxybutyrate)-Poly(Lactic Acid)-Plasticizer Blends for Three-Dimensional (3D) Printing.

This paper investigates the effect of plasticizer structure on especially the printability and mechanical and thermal properties of poly(3-hydroxybutyrate)-poly(lactic acid)-plasticizer biodegradable blends. Three plasticizers, acetyl tris(2-ethylhexyl) citrate, tris(2-ethylhexyl) citrate, and poly(ethylene glycol)bis(2-ethylhexanoate), were first checked whether they were miscible with poly(3-hydroxybutyrate)-poly(lactic acid) (PHB-PLA) blends using a kneading machine. PHB-PLA-plasticizer blends of 60-25-15 (wt.%) were then prepared using a corotating meshing twin-screw extruder, and a single screw extruder was used for filament preparation for further three-dimensional (3D) fused deposition modeling (FDM) printing. These innovative eco-friendly PHB-PLA-plasticizer blends were created with a majority of PHB, and therefore, poor mechanical properties and thermal properties of neat PHB-PLA blends were improved by adding appropriate plasticizer. The plasticizer also influences the printability of blends, which was investigated, based on our new specific printability tests developed for the optimization of printing conditions (especially printing temperature). Three-dimensional printed test samples were used for heat deflection temperature measurements and Charpy and tensile-impact tests. Plasticizer migration was also investigated. The macrostructure of 3D printed samples was observed using an optical microscope to check the printing quality and printing conditions. Tensile tests of 3D printed samples (dogbones), as well as extruded filaments, showed that measured elongation at break raised, from 21% for non-plasticized PHB-PLA reference blends to 84% for some plasticized blends in the form of filaments and from 10% (reference) to 32% for plasticized blends in the form of printed dogbones. Measurements of thermal properties (using modulated differential scanning calorimetry and oscillation rheometry) also confirmed the plasticizing effect on blends. The thermal and mechanical properties of PHB-PLA blends were improved by the addition of appropriate plasticizer. In contrast, the printability of the PHB-PLA reference seems to be slightly better than the printability of the plasticized blends.

The Covalent Tethering of Poly(ethylene glycol) to Nylon 6 Surface via N,N'-Disuccinimidyl Carbonate Conjugation: A New Approach in the Fight against Pathogenic Bacteria.

Different forms of unmodified and modified Poly(ethylene glycols) (PEGs) are widely used as antifouling and antibacterial agents for biomedical industries and Nylon 6 is one of the polymers used for biomedical textiles. Our recent study focused on an efficient approach to PEG immobilization on a reduced Nylon 6 surface via N,N'-disuccinimidyl carbonate (DSC) conjugation. The conversion of amide functional groups to secondary amines on the Nylon 6 polymer surface was achieved by the reducing agent borane-tetrahydrofuran (BH3-THF) complex, before binding the PEG. Various techniques, including water contact angle and free surface energy measurements, atomic force microscopy, scanning electron microscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy, were used to confirm the desired surface immobilization. Our findings indicated that PEG may be efficiently tethered to the Nylon 6 surface via DSC, having an enormous future potential for antifouling biomedical materials. The bacterial adhesion performances against S. aureus and P. aeruginosa were examined. In vitro cytocompatibility was successfully tested on pure, reduced, and PEG immobilized samples.

Effects of Microstripe Geometry on Guided Cell Migration.

Cell migration on material surfaces is a fundament issue in the fields of biomaterials, cell biology, tissue engineering, regenerative medicine, etc. Herein, we aim to guide cell migration by flat microstripes with significant contrast of cell adhesion and varied geometric features of the adhesive stripes. To this end, we designed and fabricated cell-adhesive arginine-glycine-aspartate (RGD) microstripes on the nonfouling poly(ethylene glycol) (PEG) background and examined the microstripe-guided adhesion and migration of a few cell types. The migration of cell clusters adhering on the RGD regions was found to be significantly affected by the widths and arc radiuses of the guided microstripes. The cells migrated fastest on the straight microstripes with width of about 20 µm, which we defined as single file confined migration (SFCM). We also checked the possible left-right asymmetric bias of cell migration guided by combinatory microstripes with alternative wavy and quasi-straight stripes under a given width, and found that the velocity of CCW (counter clockwise) migration was higher than that of CW (clockwise) migration for primary rat mesenchymal stem cells (rMSCs), whereas no left-right asymmetric bias was observed for NIH3T3 (mouse embryonic fibroblast cell line) and Hela (human cervix epithelial carcinoma cell line) cells. Comparison of migration of cells on the nanotopological stripe and smooth surfaces further confirmed the importance of cell orientation coherence for guided cell migration and strengthened the superiority of SFCM.

3D Lamellar Structure of Biomass-Based Porous Carbon Derived from Towel Gourd toward Phase Change Composites with Thermal Management and Protection.

The practical application of shape-stable phase change composites (PCCs) is beneficial to thermal energy management and energy conservation due to their superior properties. A shape-stable PCC was fabricated by incorporating poly(ethylene glycol) (PEG) with biomass-based porous carbon that was produced via freeze-drying and carbonization using a low-cost and environmentally friendly fresh towel gourd. The towel gourd derived porous carbon with the characteristics of porosity, unique three-dimensional (3D) lamellar structure, and high specific surface area allowed a high encapsulation capacity (up to 94.5 wt %) for PEG. Structural morphologies, as well as the properties of latent heat storage, thermal reliability, thermal energy management, and thermal protection ability of the fabricated shape-stable PCC, were investigated. The micromorphologies revealed that PEG molecular chains were arranged in a 3D lamellar tissue structure. The shape-stable PCC demonstrated excellent thermal reliability and a high melting latent heat of ∼164.3 J/g. The analysis of infrared thermal images indicated that the shape-stable PCC exhibited remarkable strengths in thermal energy management. The result of the thermal insulation simulation experiment proved that the shape-stable PCC had superior thermal protection ability. This study provided an innovative strategy for the design and development of shape-stable PCCs for great potential in heat-insulating protective textiles, solar thermal energy storage, energy-saving buildings, and infrared stealth of military targets.

Folic acid conjugated polymeric drug delivery vehicle for targeted cancer detection in hepatocellular carcinoma.

Targeted therapies provide increased efficiency for the detection and treatment of cancer with reduced side effects. Folate receptor (alpha subunit) is overexpressed in multiple tumors including liver cancer. In this study, we evaluated the specificity and toxicity of a folic acid-containing drug delivery vehicle (DDV) in a hepatocellular carcinoma (HCC) model. The DDV was prepared with two units each of folic acid (FA) and fluorescein isothiocyanate (FITC) molecules and conjugated to a central poly (ethylene glycol) (PEG) core via a modified chemo-enzymatic synthetic process. Rat hepatoma (N1S1) and human monocytic (U937) cell lines were used for cell culture-based assays and tested for DDV uptake and toxicity. Folate receptor expressions in liver tissues and cell lines were verified using standard immunohistochemistry techniques. Rat HCC model was used for in vivo assessment. The DDV was injected via intra-arterial or intravenous methods and imaged with IVIS spectrum in vivo imaging system. Strong signals of FITC in the liver tumor region correlated to targeted DDV uptake. The use of PEG enhanced water-solubility and provided flexibility for the interaction of FA ligands with multiple cell surface folate receptors that resulted in increased specific uptake. Our study suggested that PEG incorporation and folate targeting via intra-arterial approach is an efficient strategy for targeted delivery in HCC therapy.

Toxicity and immunogenicity concerns related to PEGylated-micelle carrier systems: a review.

Polymeric-micelle carrier systems have emerged as a novel drug-carrier system and have been actively studied for anticancer drug targeting. In contrast, toxicological and immunological concerns related to not only polymeric-micelle carrier systems, but also other nanocarrier systems, have received little attention owing to researchers' focus on therapeutic effects. However, in recent clinical contexts, biopharmaceuticals' effects on immune responses have come to light, requiring that researchers substantively explore the potential negative side effects of nanocarrier systems and of therapeutic proteins in order to develop nanocarrier systems suitable for clinical use. The present review describes current insights into both toxicological and immunological issues regarding polymeric-micelle carrier systems. The review focuses on immunogenicity issues of polymeric-micelle carrier systems possessing poly(ethylene glycol) (PEG). We conclude that PEG-related immunogenicity is deeply related to characteristics of a counterpart block of PEG-conjugates, and we propose future directions for addressing this unresolved issue.