Maleimide Functional Groups Research Articles

Influence of Controlled Chirality on the Crystallization of Maleimide-Functionalized 3,4-Ethylenedioxythiophene (EDOT-MA) Monomers.

Conjugated poly(alkoxythiophenes) such as poly(3,4-ethylenedioxythiophene) (PEDOT) have attracted considerable interest for use in a variety of applications such as biomedical devices, energy storage, and chemical sensing. Functionalized versions of the 3,4-ethylenedioxythiophene (EDOT) monomer make it possible to create polymers with properties tailored for specific applications. The maleimide functional group shows particular promise due to the wide variety of chemical modifications that it can undergo. Here, we examine the role that control of the chirality of the maleimide (MA) substituent has on the crystal structure and crystallization of the EDOT-MA monomer. We describe a method for the synthesis of a homochiral (S) variant of EDOT-MA and compare its crystallography, morphology, and thermal properties to that of the (R,S) EDOT-MA racemic compound. The conformation of the EDOT-MA molecule was substantially different, with the molecules adopting an "L" shape in the homochiral crystal, while in the racemic crystals, they were more colinear. The thermal stability of the homochiral crystals (Tm = 128.6 °C) was slightly higher than the racemic ones (Tm = 102.8 °C). We expect these results to be important in better understanding the solid-state assembly of the corresponding polymers prepared from these monomers.

Enhancing the Activity of Surface Immobilized Antimicrobial Peptides Using Thiol-Mediated Tethering to Poly(ethylene glycol).

Considering the need for versatile surface coatings that can display multiple bioactive signals and chemistries, the use of more novel surface modification methods is starting to emerge. Thiol-mediated conjugation of biomolecules is shown to be quite advantageous for such purposes due to the reactivity and chemoselectivity of thiol functional groups. Herein, the immobilization of poly(ethylene glycol) (PEG) and antimicrobial peptides (AMPs) to silica colloidal particles based on thiol-mediated conjugation techniques, along with an assessment of the antimicrobial potential of the functionalized particles against Pseudomonas aeruginosa and Staphylococcus aureus is investigated. Immobilization of PEG to thiolated Si particles is performed by either a two-step thiol-ene "photo-click" reaction or a "one-pot" thiol-maleimide type conjugation using terminal acrylate or maleimide functional groups, respectively. It is demonstrated that both immobilization methods result in a significant reduction in the number of viable bacterial cells compared to unmodified samples after the designated incubation periods with the PEG-AMP-modified colloidal suspensions. These findings provide a promising outlook for the fabrication of multifunctional surfaces based upon the tethering of PEG and AMPs to colloidal particles through thiol-mediated biocompatible chemistry, which has potential for use as implant coatings or as antibacterial formulations that can be incorporated into wound dressings to prevent or control bacterial infections.

A novel self-healing and removable hexagonal boron nitride/epoxy coating with excellent anti-corrosive property based on Diels-Alder reaction

The coatings which are able to protect the metal from being corroded by the medium in their service life while are easy to be removed when the regular maintenances and refurbishment of the coatings are carried out are in high demand. However, the relevant researches are few. In this article, a novel hexagonal boron nitride/epoxy anti-corrosive coating with self-healing, removable and recycled abilities were designed. These coatings which were totally dynamic cross-linked were synthesized by the Diels-Alder reaction between a modified hexagonal boron nitride with maleimide functional groups and epoxy containing both furan and epoxide functional groups. The structures of the epoxy composites were fully characterized. Their thermal properties, self-healing abilities, and removeable properties were also explored. The systematic study on the anti-corrosive properties of the coatings was carried out. An inhibition efficiency of 97.2 % could be realized by the sample of m-hBN-OH/epoxy98–2, in which 2 % of the cross-linking degree was provided by the functional hBN fillers. All the research results revealed that this novel coating could serve as the long durable anti-corrosive material in its service life while was easy to be removed when the regular refurbishment was conducted.

"Clickable" Polymer Brush Interfaces: Tailoring Monovalent to Multivalent Ligand Display for Protein Immobilization and Sensing.

Facile and effective functionalization of the interface of polymer-coated surfaces allows one to dictate the interaction of the underlying material with the chemical and biological analytes in its environment. Herein, we outline a modular approach that would enable installing a variety of “clickable” handles onto the surface of polymer brushes, enabling facile conjugation of various ligands to obtain functional interfaces. To this end, hydrophilic anti-biofouling poly(ethylene glycol)-based polymer brushes are fabricated on glass-like silicon oxide surfaces using reversible addition–fragmentation chain transfer (RAFT) polymerization. The dithioester group at the chain-end of the polymer brushes enabled the installation of azide, maleimide, and terminal alkene functional groups, using a post-polymerization radical exchange reaction with appropriately functionalized azo-containing molecules. Thus, modified polymer brushes underwent facile conjugation of alkyne or thiol-containing dyes and ligands using alkyne–azide cycloaddition, Michael addition, and radical thiol–ene conjugation, respectively. Moreover, we demonstrate that the radical exchange approach also enables the installation of multivalent motifs using dendritic azo-containing molecules. Terminal alkene groups containing dendrons amenable to functionalization with thiol-containing molecules using the radical thiol–ene reaction were installed at the interface and subsequently functionalized with mannose ligands to enable sensing of the Concanavalin A lectin.

Carborane–Bodipy Conjugates: Synthesis and Characterization

A series of new carborane–BODIPY conjugates bearing succinimide–triazole or maleimide functional groups are prepared from synthetically available amino-substituted BODIPYs. The resulting compounds are characterized by UV–vis, IR, and NMR spectroscopy as well as mass spectrometry.

Microfluidic Fabrication of Core-Shell Microcapsules carrying Human Pluripotent Stem Cell Spheroids.

Three-dimensional (3D) or spheroid cultures of human pluripotent stem cells (hPSCs) offer the benefits of improved differentiation outcomes and scalability. In this paper, we describe a strategy for the robust and reproducible formation of hPSC spheroids where a co-axial flow focusing device is utilized to entrap hPSCs inside core-shell microcapsules. The core solution contained single cell suspension of hPSCs and was made viscous by the incorporation of high molecular weight poly(ethylene glycol) (PEG) and density gradient media. The shell stream comprised of PEG-4 arm-maleimide or PEG-4-Mal and flowed alongside the core stream toward two consecutive oil junctions. Droplet formation occurred at the first oil junction with shell solution wrapping itself around the core. Chemical crosslinking of the shell occurred at the second oil junction by introducing a di-thiol crosslinker (1,4-dithiothreitol or DTT) to these droplets. The crosslinker reacts with maleimide functional groups via click chemistry, resulting in the formation of a hydrogel shell around the microcapsules. Our encapsulation technology produced 400 µm diameter capsules at a rate of 10 capsules per second. The resultant capsules had a hydrogel shell and an aqueous core that allowed single cells to rapidly assemble into aggregates and form spheroids. The process of encapsulation did not adversely affect the viability of hPSCs, with >95% viability observed 3 days post-encapsulation. For comparison, hPSCs encapsulated in solid gel microparticles (without an aqueous core) did not form spheroids and had <50% viability 3 days after encapsulation. Spheroid formation of hPSCs inside core-shell microcapsules occurred within 48 h after encapsulation, with the spheroid diameter being a function of cell inoculation density. Overall, the microfluidic encapsulation technology described in this protocol was well-suited for hPSCs encapsulation and spheroid formation.

A Facile Procedure for One-Pot Stable Conjugation of Two Proglucagon Cysteine-Containing Peptide Analogs.

Optimization of peptides for therapeutic purposes often includes chemical conjugation or modification with substituents that serve to broaden pharmacology or improve pharmacokinetics. We report a convenient and rapid procedure for one-pot, site-specific conjugation of two cysteine-containing peptides that utilizes a bivalent linker comprising maleimide and iodoacetyl functional groups. Following maleimide-mediated peptide conjugation the linker was converted from an unstable thiosuccinimide to a stable thioether bond suitable for biological study by mild aqueous hydrolysis. The procedure is exemplified by peptide-peptide, peptide-small molecule, and peptide-fatty acid conjugations. The method provides a facile approach to search for enhanced biological outcomes through additive and sustained peptide pharmacology unencumbered by the prospect of chemical rearrangement in the course of biological study.

The Influence of the Furan and Maleimide Stoichiometry on the Thermoreversible Diels–Alder Network Polymerization

In recent work, the thermoreversible Diels–Alder reaction between furan and maleimide functional groups has been studied extensively in the context of self-healing elastomers and thermosets. To elaborate the influence of the stoichiometric ratio between the maleimide and furan reactive groups on the thermomechanical properties and viscoelastic behavior of formed reversible covalent polymer networks, a series of Diels–Alder-based networks with different stoichiometric ratios was synthesized. Differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA) and dynamic rheology measurements were performed on the reversible polymer networks, to relate the reversible network structure to the material properties and reactivity. Such knowledge allows the design and optimization of the thermomechanical behavior of the reversible networks for intended applications. Lowering the maleimide-to-furan ratio creates a deficit of maleimide functional groups, resulting in a decrease in the crosslink density of the system, and a consequent decrease in the glass transition temperature, Young’s modulus, and gel transition temperature. The excess of unreacted furan in the system results in faster reaction and healing kinetics and a shift of the reaction equilibrium.

Covalent conjugation of single-walled carbon nanotube with CYP101 mutant for direct electrocatalysis

Covalent linkage between the single-walled carbon nanotube (SWCNT) and CYP101 through a specific site of the enzyme can provide a novel method of designing efficient enzyme electrodes using this prototype cytochrome P450 enzyme. We have chemically modified the SWCNT with linker 4-carboxy phenyl maleimide (CPMI) containing maleimide functional groups. The enzyme was covalently attached on to the SWCNT through the maleimide group of the linker (CPMI) to the thiolate group of the surface exposed Cys 58 or Cys 136 of the CYP101 forming a covalently immobilized protein on the nanotube. Thin film of the modified SWCNT-CPMI-CYP101conjugate was made on a glassy carbon (GC) electrode. Direct electrochemistry of the substrate (camphor)-bound enzyme was studied using this immobilized enzyme electrode system and the redox potential was found to be −320mV vs Ag/AgCl (3 M KCl), which agrees with the redox potential of the substrate bound enzyme reported earlier.The electrochemically driven enzymatic mono-oxygenation of camphor by this immobilized enzyme electrode system was studied by measurement of the catalytic current at different concentrations of camphor. The catalytic current was found to increase with increasing concentration of camphor in presence of oxygen. The product formed during the catalysis was identified by mass-spectrometry as hydroxy-camphor.

Release of Anticancer Agents in the Tumor Microenvironment Using Cathepsin B and Cathepsin L Cleavable Drug‐Linker Constructs

Cysteine cathepsins are a family of cysteine proteases that are normally localized to the lysosome for maintaining homeostasis. In a number of highly invasive cancer cell lines and malignant tumors, cathepsins L and B are highly upregulated and are secreted into the extracellular matrix as pro-enzymes. Upon activation, they promote remodeling of the extracellular matrix and cancer progression and metastasis. A number of studies have demonstrated that cathepsins L and B are overexpressed in breast, ovarian, lung, and colon cancer. The goal is to use the extracellular proteolytic activity of cathepsin L and/or cathepsin B to cleave drug-linker constructs in the tumor microenvironment to release potent anticancer agents. Drug-linker constructs in this study consist of a maleimide functional group for attachment of a protein tumor-targeting agent (such as an antibody), a protease cleavable linker, and a cytotoxic effector (payload). Several pre-validated benzosuberene- and dihydronaphthalene-based effectors bind to tubulin at the colchicine binding site and are effective inhibitors of tubulin polymerization into microtubules. They demonstrate profound cytotoxicity (low nM to pM) against a wide-spectrum of human cancer cell lines. In addition to their antimitotic activity, they exhibit dual-mechanism of action and function as powerful vascular disrupting agents (VDAs), imparting widespread damage to tumor-associated vasculature that results in blood flow shutdown and massive tumor necrosis. The hypothesis is that cathepsin B and/or cathepsin L will effectively and selectively cleave these drug-linker constructs in the tumor microenvironment, thus facilitating release of the potent dual-mechanism effector agents leading to inhibition of tumor growth and metastasis. In this study, substate specificity and cleavage rates were evaluated for a series of benzosuberene- and dihydronaphthalene-based drug-linker constructs incorporating L-Val-L-Cit and other dipeptides. Assay conditions were optimized for each enzyme. Standard curves were obtained for drug-linker constructs and effectors using reversed-phase HPLC. For drug-linker constructs, the maleimide head group was first de-activated by the thiol agent, N-acetyl-L cysteine (NAC), and the products were incubated for variable times with either cathepsin L or B. After dilution of the reaction mixtures with acetonitrile, the release of effector was evaluated by HPLC. Using standard curves, the percent cleavage and the recovery were calculated for each reaction in these rate studies. The L-Val-L-Cit dipeptide linker was cleaved by both cathepsin B and cathepsin L. Rates of cleavage of drug-linker constructs with a series of different dipeptides replacing L-Val-L-Cit were determined.

Vapor-Phase Fabrication of a Maleimide-Functionalized Poly-p-xylylene with a Three-Dimensional Structure

A vapor-phase process, involving the sublimation of an ice substrate/template and the vapor deposition of a maleimide-functionalized poly-p-xylylene, has been reported to synthesize an advanced porous material, with readily clickable chemical interface properties, to perform a Michael-type addition of a maleimide functionality for conjugation with a thiol group. In contrast to the conventional chemical vapor deposition of poly-p-xylylenes on a solid surface that forms thin film coatings, the process reported herein additionally results in deposition on a dynamic and sublimating ice surface (template), rendering the construction of a three-dimensional, porous, maleimide-functionalized poly-p-xylylene. The process seamlessly exploits the refined chemical vapor deposition polymerization from maleimide-substituted [2,2]paracyclophane and ensures the preservation and transformation of the maleimide functionality to the final porous poly-p-xylylene products. The functionalization and production of a porous maleimide-functionalized poly-p-xylylene were completed in a single step, thus avoiding complicated steps or post-functionalization procedures that are commonly seen in conventional approaches to produce functional materials. More importantly, the equipped maleimide functionality provides a rapid and efficient route for click conjugation toward thiol-terminated molecules, and the reaction can be performed under mild conditions at room temperature in a water solution without the need for a catalyst, an initiator, or other energy sources. The introduced vapor-based process enables a straightforward synthesis approach to produce not only a pore-forming structure of a three-dimensional material, but also an in situ-derived maleimide functional group, to conduct a covalent click reaction with thiol-terminal molecules, which are abundant in biological environments. These advanced materials are expected to have a wide variety of new applications.

Pure redox-sensitive paclitaxel–maleimide prodrug nanoparticles: Endogenous albumin-induced size switching and improved antitumor efficiency

A commercial albumin-bound paclitaxel nano-formulation has been considered a gold standard against breast cancer. However, its application still restricted unfavorable pharmacokinetics and the immunogenicity of exogenous albumin carrier. Herein, we report an albumin-bound tumor redox-responsive paclitaxel prodrugs nano-delivery strategy. Using diverse linkages (thioether bond and disulfide bond), paclitaxel (PTX) was conjugated with an albumin-binding maleimide (MAL) functional group. These pure PTX prodrugs could self-assemble to form uniform and spherical nanoparticles (NPs) in aqueous solution without any excipients. By immediately binding to blood circulating albumin after intravenous administration, NPs are rapidly disintegrated into small prodrug/albumin nanoaggregates in vivo, facilitating PTX prodrugs accumulation in the tumor region via albumin receptor-mediated active targeting. The tumor redox dual-responsive drug release property of prodrugs improves the selectivity of cytotoxicity between normal and cancer cells. Moreover, disulfide bond-containing prodrug/albumin nanoaggregates exhibit long circulation time and superior antitumor efficacy in vivo. This simple and facile strategy integrates the biomimetic characteristic of albumin, tumor redox-responsive on-demand drug release, and provides new opportunities for the development of the high-efficiency antitumor nanomedicines.

Toward the Clinical Development and Validation of a Thy1-Targeted Ultrasound Contrast Agent for the Early Detection of Pancreatic Ductal Adenocarcinoma.

We recombinantly expressed the Thy1-scFv with a carboxy-terminus cysteine residue to facilitate its thioether conjugation to the PEGylated MBs presenting with maleimide functional groups. After the scFv-MB conjugations, we tested binding activity of the MBThy1-scFv to MS1 cells overexpressing human Thy1 (MS1Thy1) under liquid shear stress conditions in vitro using a flow chamber setup at 0.6 mL/min flow rate, corresponding to a wall shear stress rate of 100 seconds, similar to that in tumor capillaries. For in vivo Thy1 US molecular imaging, MBThy1-scFv was tested in the transgenic mouse model (C57BL/6J - Pdx1-Cre; KRas; Ink4a/Arf) of PDAC and in control mice (C57BL/6J) with L-arginine-induced pancreatitis or normal pancreas. To facilitate its clinical feasibility, we further produced Thy1-scFv without the bacterial fusion tags and confirmed its recognition of human Thy1 in cell lines by flow cytometry and in patient PDAC frozen tissue sections of different clinical grades by immunofluorescence staining. Under shear stress flow conditions in vitro, MBThy1-scFv bound to MS1Thy1 cells at significantly higher numbers (3.0 ± 0.8 MB/cell; P < 0.01) compared with MBNontargeted (0.5 ± 0.5 MB/cell). In vivo, MBThy1-scFv (5.3 ± 1.9 arbitrary units [a.u.]) but not the MBNontargeted (1.2 ± 1.0 a.u.) produced high US molecular imaging signal (4.4-fold vs MBNontargeted; n = 8; P < 0.01) in the transgenic mice with spontaneous PDAC tumors (2-6 mm). Imaging signal from mice with L-arginine-induced pancreatitis (n = 8) or normal pancreas (n = 3) were not significantly different between the two MB constructs and were significantly lower than PDAC Thy1 molecular signal. Clinical-grade scFv conjugated to Alexa Fluor 647 dye recognized MS1Thy1 cells but not the parental wild-type cells as evaluated by flow cytometry. More importantly, scFv showed highly specific binding to VEGFR2-positive vasculature and fibroblast-like stromal components surrounding the ducts of human PDAC tissues as evaluated by confocal microscopy. Our findings summarize the development and validation of a clinically relevant Thy1-targeted US contrast agent for the early detection of human PDAC by US molecular imaging.

The joint effect of amine and maleimide functional group in aminomaleimide on the curing kinetics and mechanical properties of epoxy resins

A new epoxy curing system, combining amine and maleimide functionality into a single molecule, was introduced to broaden current state of the art as regards epoxy, amine and maleimide systems. Curing agent aminomaleimide was tested in the curing process of several aromatic and aliphatic epoxies. Prepared mixtures in different weight (molar) ratios were investigated by nonisothermal differential scanning calorimetry to study and compare curing kinetics of different epoxies. The apparent activation energy was determined by Kissinger method, while Friedman method accompanied by Malék statistical approach was used in confirming the autocatalytic nature of epoxy curing and additional maleimide polymerization at the excess amount of aminomaleimide. Thermo-mechanical properties were determined by dynamic mechanical analysis and the effect of aminomaleimide curing agent compared to curing agent containing only amino functional groups was evaluated. Aminomaleimide showed improvement in the glass transition temperatures and higher char yields due to the involvement of maleimide moiety in the curing process. In overall, aminomaleimide showed the positive one-molecule joint effect of the amino group, behaving as an accelerator, and maleimide group, a mechanical properties enhancer.

A novel shape memory-assisted and thermo-induced self-healing boron nitride/epoxy composites based on Diels–Alder reaction

Hexagonal boron nitride (hBN), as one of the two-dimensional (2D) materials, possesses many excellent properties like others. Herein, we report a novel self-healing epoxy filled with hBN. High compatibility between hBN and the epoxy matrix was obtained by the modification of hBN with silane coupling agent (Mi-Si). At the meantime, excellent self-healing behavior was achieved by retro Diels–Alder (r-DA) reaction between the maleimide functional group in the modified hBN (m-hBN-OH) and the added furfurylamine. Besides, the inadequate curing of epoxy led to the glass transition temperature (Tg), which is also seemed as the transition temperature for the shape memory of the epoxy, below the r-DA reaction temperature, and endowed the system with the shape memory-assisted self-healing properties. The m-hBN-OH was characterized by Fourier transform infrared spectra, nuclear magnetic resonance (1H-NMR) spectra, X-ray diffraction experiments, X-ray photoelectron spectroscopy measurements and so on. The new m-hBN-OH modifier was prepared with the optimized Mi-Si/hBN-OH weight ratio of 3.0, which could both improve the thermal property and achieve better thermal conductivity. This designed m-hBN-OH/epoxy could actually show ideal self-healing properties due to the shape memory-assisted self-healing effect. The thermal conductivity of the neat epoxy resin and the m-hBN-OH/epoxy was 0.2156 W m−1 K−1 and 0.4358 W m−1 K−1, respectively. As a novel material with efficient thermal conductivity, hBN made great contribution to the thermally induced shape memory and self-healing property. Systematic researches reveal that the composites are promising as long durable thermal interface materials, anti-scratch materials and so on.

Fabrication of Patterned Hydrogel Interfaces: Exploiting the Maleimide Group as a Dual Purpose Handle for Cross-Linking and Bioconjugation.

Functional hydrogels that can be obtained through facile fabrication procedures and subsequently modified using straightforward reagent-free methods are indispensable materials for biomedical applications such as sensing and diagnostics. Herein a novel hydrogel platform is obtained using polymeric precursors containing the maleimide functional group as a side chain. The maleimide groups play a dual role in fabrication of functional hydrogels. They enable photochemical cross-linking of the polymers to yield bulk and patterned hydrogels. Moreover, the maleimide group can be used as a handle for efficient functionalization using the thiol-maleimide conjugation and Diels-Alder cycloaddition click reactions. Obtained hydrogels are characterized in terms of their morphology, water uptake capacity, and functionalization. Micropatterned hydrogels are obtained under UV-irradiation using a photomask to obtain reactive micropatterns, which undergo facile functionalization upon treatment with thiol-containing functional molecules such as fluorescent dyes and bioactive ligands. The maleimide group also undergoes conjugation through the Diels-Alder reaction, where the attached molecule can be released through thermal treatment via the retro Diels-Alder reaction. The antibiofouling nature of these hydrogel micropatterns enables efficient ligand-directed biomolecular immobilization, as demonstrated by attachment of streptavidin-coated quantum dots.

Improvement of Mechanical and Self-Healing Properties for Polymethacrylate Derivatives Containing Maleimide Modified Graphene Oxide.

In this paper, a self-healable nanocomposite based on the Diels-Alder reaction is developed. A graphene-based nanofiller is introduced to improve the self-healing efficiency, as well as the mechanical properties of the nanocomposite. Graphene oxide (GO) is modified with maleimide functional groups, and the maleimide-modified GO (mGO) enhanced the compatibility of the polymer matrix and nanofiller. The tensile strength of the nanocomposite containing 0.030 wt% mGO is improved by 172%, compared to that of a polymer film incorporating both furan-functionalized polymer and bismaleimide without any nanofiller. Moreover, maleimide groups of the surface on mGO participate in the Diels-Alder reaction, which improves the self-healing efficiency. The mechanical and self-healing properties are significantly improved by using a small amount of mGO.

Preparation and Characterization of Thermal and pH Dual Sensitive Hydrogel Based on 1,3‐Dipole Cycloaddition Reaction

In this study, thermal and pH dual sensitive hydrogels were prepared via Cu‐free 1,3‐dipole cycloaddition between two copolymers which were modified by azide and maleimide functional groups, respectively. First, the thermally sensitive terpolymers were fabricated via conventional free‐radical polymerization of N‐isopropylacrylamide, hydroxyethyl methacrylate (HEMA), and N,N‐dimethylacrylamide (DMA). Then, polymeric dipolarophiles were synthesized via the esterification between the above terpolymers and N‐maleoyl alanine. Similarly, the pH‐sensitive terpolymers were also fabricated via conventional free‐radical polymerization of 4‐vinylpyridine, HEMA, and DMA, and then, polymeric dipoles were acquired via the decoration of the as‐prepared terpolymers with 2‐azidoacetic acid. Afterward, the smart hydrogels were fabricated via the aqueous 1,3‐dipole cycloaddition reaction between the as‐prepared polymeric dipolarophiles and dipoles without the use of catalysts. The results of swelling measurements confirm that the hydrogels possessed thermal and pH dual sensitivity. Moreover, the investigation of the behavior of oscillatory swelling shrinking indicates their sensitivity to temperature and pH was reversible and repeatable, which is of great significance for the repeated use of the prepared hydrogels. The proposed strategy demonstrates a great application prospects in the preparation of hydrogels as there were no catalysts and organic solvents employed. POLYM. ENG. SCI., 60:917–924, 2020. © 2020 Society of Plastics Engineers

Macromolecular design of a reversibly crosslinked shape-memory material with thermo-healability

A new thermoresponsive self-healing polymer thermoset ((1.5M/F)DA-PDMS-PU) based on the Diels–Alder (DA) reaction between furan and maleimide groups was developed. The material exhibited glass temperature induced shape memory effect that brings crack faces into intimate contact, enabling the reformation of DA bridges located in the crack surfaces. In addition, the incorporation PDMS segments and excess maleimide functional groups besides DA bridges in the network promotes the mobility of dynamic groups and the healing reaction, therefore increasing the ability of the material to heal damages at a mild temperature. Scratch healing was possible via a one-step heating process at a moderate temperature of 60 °C for 4 h, reaching a tensile strength recovery of above 85%.

Anti-DLL4 VNAR targeted nanoparticles for targeting of both tumour and tumour associated vasculature.

Whilst there is an extensive body of preclinical nanomedicine research, translation to clinical settings has been slow. Here we present a novel approach to the targeted nanoparticle (NP) concept: utilizing both a novel targeting ligand, VNAR (Variable New Antigen Receptor), a shark-derived single chain binding domain, and an under-investigated target in delta-like ligand 4 (DLL4). We describe the development of an anti-DLL4 VNAR and the site-specific conjugation of this to poly(lactic-co-glycolic) acid PEGylated NPs using surface maleimide functional groups. These nanoconjugates were shown to specifically bind DLL4 with high affinity and were preferentially internalized by DLL4-expressing pancreatic cancer cell lines and endothelial cells. Furthermore, a distinct anti-angiogenic effect endowed by the anti-DLL4 VNAR was evident in in vitro tubulogenic assays. Taken together these findings highlight the potential of anti-DLL4 targeted polymeric NPs as a novel therapeutic approach in pancreatic cancer.