Dextran-block-poly(benzyl glutamate) block copolymers via aqueous polymerization-induced self-assembly.

Combining polysaccharides with polypeptides enables growth of diverse nanostructures with minimal toxicity, low immune response, and potential biodegradability. However, examples of nanostructures combining polysaccharides with polypeptides are limited due to synthetic difficulties and related issues of solubility, purification, and characterization, with previous reports of polysaccharide-block-polypeptide block copolymers requiring methods such as polymer-polymer coupling and post-polymerization modifications paired with difficult purification steps. Here, we synthesized dextran-block-poly(benzyl glutamate) block copolymers in water via polymerization-induced self-assembly (PISA) to form nanostructures in situ, studying their morphologies using experimental methods and molecular modeling.

Regulating HS release from self-assembled peptide HS-donor conjugates using cysteine derivatives.

Self-assembled peptides provide a modular and diverse platform for drug delivery, and innovative delivery methods are needed for delivery of hydrogen sulfide (HS), an endogenous signaling molecule (gasotransmitter) with significant therapeutic potential. Of the available types of HS donors, peptide/protein HS donor conjugates (PHDCs) offer significant versatility. Here we discuss the design, synthesis, and in-depth study of a PHDC containing three covalently linked components: a thiol-triggered HS donor based on an -aroylthiooxime (SATO), a GFFF tetrapeptide, and a tetraethylene glycol (TEG) dendron.

Stimuli-Responsive Polymers at the Interface with Biology.

There has been growing interest in polymeric systems that break down or undergo property changes in response to stimuli. Such polymers can play important roles in biological systems, where they can be used to control the release of therapeutics, modulate imaging signals, actuate movement, or direct the growth of cells. In this Perspective, after discussing the most important stimuli relevant to biological applications, we will present a selection of recent exciting developments.

NO- and HS- releasing nanomaterials: A crosstalk signaling pathway in cancer.

The gasotransmitters nitric oxide (NO) and hydrogen sulfide (HS) play important roles not only in maintaining physiological functions, but also in pathological conditions and events. Importantly, these molecules show a complex interplay in cancer biology, demonstrating both tumor-promoting and anti-tumor activities depending on their concentration, flux, and the environmental redox state. Additionally, various cell types respond differently to NO and HS.

Polymer Characterization by Size-Exclusion Chromatography with Multi-Angle Light Scattering (SEC-MALS): A Tutorial Review.

This tutorial review presents the theory and application of SEC-MALS with minimal equations and a focus on synthetic polymer characterization, serving as an entry point for polymer scientists who want to learn more about SEC-MALS. We discuss the principles of static light scattering, outline its capability to generate absolute weight-average molar mass values, and extend its application to SEC-MALS. Practical elements are emphasized, enabling researchers to appreciate how values for , and are determined in an SEC-MALS experiment and how experimental conditions and input values, such as the specific refractive index increment ( ), influence the results.

Synthesis and real-time characterization of self-healing, injectable, fast-gelling hydrogels based on alginate multi-reducing end polysaccharides (MREPs).

Polysaccharide-based hydrogels are promising for many biomedical applications including drug delivery, wound healing, and tissue engineering. We illustrate herein self-healing, injectable, fast-gelling hydrogels prepared from multi-reducing end polysaccharides, recently introduced by the Edgar group. Simple condensation of reducing ends from multi-reducing end alginate (M-Alg) with amines from polyethylene imine (PEI) in water affords a dynamic, hydrophilic polysaccharide network.

Design, Synthesis, and Antifungal Activity of 3-Substituted-2()-Oxaboroles.

Next generation antimicrobial therapeutics are desperately needed as new pathogens with multiple resistance mechanisms continually emerge. Two oxaboroles, tavaborole and crisaborole, were recently approved as topical treatments for onychomycosis and atopic dermatitis, respectively, warranting further studies into this privileged structural class. Herein, we report the antimicrobial properties of 3-substituted-2()-oxaboroles, an unstudied family of medicinally relevant oxaboroles.

Using Redox-Switchable Polymerization Catalysis to Synthesize a Chemically Recyclable Thermoplastic Elastomer.

In an effort to synthesize chemically recyclable thermoplastic elastomers, a redox-switchable catalytic system was developed to synthesize triblock copolymers containing stiff poly(lactic acid) (PLA) end blocks and a flexible poly(tetrahydrofuran-co-cyclohexene oxide) (poly(THF-co-CHO) copolymer as the mid-block. The orthogonal reactivity induced by changing the oxidation state of the iron-based catalyst enabled the synthesis of the triblock copolymers in a single reaction flask from a mixture of monomers. The triblock copolymers demonstrated improved flexibility compared to poly(l-lactic acid) (PLLA) and thermomechanical properties that resemble thermoplastic elastomers, including a rubbery plateau in the range of -60 to 40 °C.

Endothelial deletion of EPH receptor A4 alters single-cell profile and Tie2/Akap12 signaling to preserve blood-brain barrier integrity.

Neurobiological consequences of traumatic brain injury (TBI) result from a complex interplay of secondary injury responses and sequela that mediates chronic disability. Endothelial cells are important regulators of the cerebrovascular response to TBI. Our work demonstrates that genetic deletion of endothelial cell (EC)-specific EPH receptor A4 (EphA4) using conditional and knockout (KO) mice promotes blood-brain barrier (BBB) integrity and tissue protection, which correlates with improved motor function and cerebral blood flow recovery following controlled cortical impact (CCI) injury.

Activating hidden signals by mimicking cryptic sites in a synthetic extracellular matrix.

Cryptic sites are short signaling peptides buried within the native extracellular matrix (ECM). Enzymatic cleavage of an ECM protein reveals these hidden peptide sequences, which interact with surface receptors to control cell behavior. Materials that mimic this dynamic interplay between cells and their surroundings via cryptic sites could enable application of this endogenous signaling phenomenon in synthetic ECM hydrogels.

Hydrogels for Gasotransmitter Delivery: Nitric Oxide, Carbon Monoxide, and Hydrogen Sulfide.

Gasotransmitters, gaseous signaling molecules including nitric oxide (NO), carbon monoxide (CO), and hydrogen sulfide (H S), maintain myriad physiological processes. Low levels of gasotransmitters are often associated with specific problems or diseases, so NO, CO, and H S hold potential in treating bacterial infections, chronic wounds, myocardial infarction, ischemia, and various other diseases. However, their clinical applications as therapeutic agents are limited due to their gaseous nature, short half-life, and broad physiological roles.

Supramolecular Peptide Nanostructures Regulate Catalytic Efficiency and Selectivity.

We report three constitutionally isomeric tetrapeptides, each comprising one glutamic acid (E) residue, one histidine (H) residue, and two lysine (K ) residues functionalized with side-chain hydrophobic S-aroylthiooxime (SATO) groups. Depending on the order of amino acids, these amphiphilic peptides self-assembled in aqueous solution into different nanostructures:nanoribbons, a mixture of nanotoroids and nanoribbons, or nanocoils. Each nanostructure catalyzed hydrolysis of a model substrate, with the nanocoils exhibiting the greatest rate enhancement and the highest enzymatic efficiency.

Enzyme-Triggered Chemodynamic Therapy via a Peptide-H S Donor Conjugate with Complexed Fe.

Inducing high levels of reactive oxygen species (ROS) inside tumor cells is a cancer therapy method termed chemodynamic therapy (CDT). Relying on delivery of Fenton reaction promoters such as Fe , CDT takes advantage of overproduced ROS in the tumor microenvironment. We developed a peptide-H S donor conjugate, complexed with Fe , termed AAN-PTC-Fe .

N-thiocarboxyanhydrides, amino acid-derived enzyme-activated HS donors, enhance sperm mitochondrial activity in presence and absence of oxidative stress.

Background: Hydrogen sulfide (HS) donors are crucial tools not only for understanding the role of HS in cellular function but also as promising therapeutic agents for oxidative stress-related diseases. This study aimed to explore the effect of amino acid-derived N-thiocarboxyanhydrides (NTAs), which release physiological HS levels in the presence of carbonic anhydrase, on porcine sperm function during short-term incubation with and without induced oxidative stress. For this purpose, we employed two HS-releasing NTAs with release half-lives (t) in the range of hours that derived from the amino acids glycine (Gly-NTA) or leucine (Leu-NTA).

Electrospun Scaffolds Functionalized with a Hydrogen Sulfide Donor Stimulate Angiogenesis.

Tissue-engineered constructs are currently limited by the lack of vascularization necessary for the survival and integration of implanted tissues. Hydrogen sulfide (HS), an endogenous signaling gas (gasotransmitter), has been recently reported as a promising alternative to growth factors to mediate and promote angiogenesis in low concentrations. Yet, sustained delivery of HS remains a challenge.

Poly(β-Cyclodextrin) Prepared by Ring-Opening Metathesis Polymerization Enables Creation of Supramolecular Polymeric Networks.

The controlled synthesis of polymers containing densely grafted cyclodextrin units has proven challenging due to the steric hindrance of these cyclic oligosaccharides. In this study, we report the controlled synthesis of poly(β-cyclodextrin) [poly(β-CD)] through ring-opening metathesis polymerization (ROMP) using Grubbs third-generation catalyst. Molecular weights of >10 g/mol were obtained with dispersity values () of ≤1.

pH-Responsive Self-Assembling Peptide-Based Biomaterials: Designs and Applications.

Stimuli-responsive peptide-based biomaterials are increasingly gaining interest for various specific and targeted treatments, including drug delivery and tissue engineering. Among all stimuli, pH can be especially useful because endogenous pH changes are often associated with abnormal microenvironments. pH-Responsive amino acids and organic linkers can be easily incorporated into peptides that self-assemble into various nanostructures.

Green-light-responsive metal-organic frameworks for colorectal cancer treatment.

Herein, the synthetic methods for preparation of a novel light-responsive metal-organic framework (MOF) UiO-AZB-F are outlined. Upon irradiation with green light, the framework demonstrates controlled release of chemotherapeutic drug cargo with simultaneous breakdown into low toxicity small molecule components.

Strong Variation of Micelle-Unimer Coexistence as a Function of Core Chain Mobility.

Polymeric micelles coexist in solution with unassembled chains (unimers). We have investigated the influence of glass transition temperature ( ) (i.e.

A Review of Chemical Tools for Studying Small Molecule Persulfides: Detection and Delivery.

Hydrogen sulfide (HS) has gained significant attention as a potent bioregulator in the redox metabolome, but it is just one of many reactive sulfur species (RSS). Recently, small molecule persulfides (structure RSSH) have emerged as RSS of particular interest due to their enhanced antioxidant abilities compared to HS and their ability to directly convert protein thiols into protein persulfides, suggesting that persulfides may have distinct physiological functions from HS. However, persulfides exhibit instability and cross-reactivity that hampers the elucidation of their precise biological roles.

Amino acid-based HS donors: -thiocarboxyanhydrides that release HS with innocuous byproducts.

A library of N-thiocarboxyanhydrides (NTAs) derived from natural amino acids with benign byproducts and controlled H2S-release kinetics is reported. Minimal acute in vitro toxicity was observed in multiple cell lines, while longer-term toxicity in cancer cells was observed, with slow-releasing donors exhibiting the greatest cytotoxic effects.