Influence of the Saccharide Structure on Cargo Loading, Thermal Properties, and Lectin Binding of Amphiphilic Glycopolymer-Polylactic Acid Block Copolymer Nanoparticles.

Stereospecific arrangements of saccharide molecules control biological recognition and binding with proteins. These properties can also be utilized in the design of biomaterials for applications such as polymeric drug delivery, where saccharides may enhance the ability to target specific cells. Glycopolymer block copolymers incorporating pendant saccharides at high concentration have potential for use in applications; however, there is a need for further evaluation of their structure-property relationships.

Bioactive Supramolecular Polymers for Skin Regeneration Following Burn Injury.

Severe deep dermal burns present a significant challenge for the clinician, often resulting in complications including infection, scarring, and potentially multisystem organ failure. The current standard of care, which involves debridement and skin coverage, has improved survival rates but remains insufficient for optimal tissue regeneration and functional recovery. Additionally, there can be limited donor skin availability with severe burns, leading to the use of skin substitutes to be applied with varying degrees of success reported.

Disulfide cross-linked redox-sensitive peptide condensates are efficient cell delivery vehicles of molecular cargo.

Biomolecular condensates (BCs) are phase-separated viscoelastic hubs within demixed solutions enriched in proteins and nucleic acids. Such condensates, also called membraneless organelles, are increasingly observed in cells and serve as transient hubs for spatial organization and compartmentalization of biomolecules. Along with the transiency of formation and dissolution, their ability to sequester molecules has inspired us to develop BCs as potential vehicles to transport and deliver molecular cargo.

Combating Reactive Oxygen Species (ROS) with Antioxidant Supramolecular Polymers.

Reactive oxygen species (ROS) are highly damaging biological molecules significantly upregulated following major injuries or diseases such as heart attack, burn injury, and stroke. Despite promising preclinical results, traditional small-molecule antioxidant therapies have had limited success in clinical applications. In this study, we employed a macromolecular approach to combat ROS, demonstrating that tethering the potent biological antioxidant, glutathione, to a peptide amphiphile effectively consumes harmful extracellular radicals while preserving antioxidant and polymeric functionality.

Amyloid Peptide-Polymer Blends with Enhanced Mechanical and Biological Properties.

Amyloid peptides are structurally diverse materials that exhibit different properties depending on their self-assembly. While they are often associated with neurodegenerative diseases, functional amyloids play important roles in nature and exhibit properties with high relevance for biomedical applications, including remarkable strength, mechanical stability, antimicrobial and antioxidant properties, low cytotoxicity, and adhesion to biotic and abiotic surfaces. Challenges in developing amyloid biomaterials include the complexity of peptide chemistry and the practical techniques required for processing amyloids into bulk materials.

Fast and Facile Synthesis of Cobalt-Doped ZIF-8 and FeO/MCC/Cobalt-Doped ZIF-8 for the Photodegradation of Organic Dyes under Visible Light.

Co-doped ZIF-8 as a water-stable visible light photocatalyst was prepared by using a one-pot, fast, cost-effective, and environmentally friendly method. The band structure of ZIF-8 was tuned through the incorporation of different percentages of cobalt to attain an optimal band gap ( ) that enables the activation of ZIF-8 under visible light and minimizes the recombination of photogenerated charge carriers. A magnetic composite of Co-doped ZIF-8 was also synthesized to facilitate catalyst recycling and reusability through the application of an external magnetic field.

Biocompatible Glycopolymer-PLA Amphiphilic Hybrid Block Copolymers with Unique Self-Assembly, Uptake, and Degradation Properties.

The self-assembly of Janus-type amphiphilic hybrid block copolymers composed of hydrophilic/hydrophobic layers has shown promise for drug encapsulation and delivery. Saccharides have previously been incorporated to improve the biocompatibility of self-assembled structures; however, glycopolymer block copolymers have been less explored, and their structure-property relationships are not well understood. In this study, novel glycopolymer-branched poly(lactic acid) (PLA) block copolymers were synthesized via thiol-ene coupling and their composition-dependent morphologies were elucidated.

Amyloid peptide - synthetic polymer blends with enhanced mechanical and biological properties.

Interest in utilizing amyloids to develop biomaterials is increasing due to their potential for biocompatibility, unique assembling morphology, mechanical stability, and biophysical properties. However, challenges include the complexity of peptide chemistry and the practical techniques required for processing amyloids into bulk materials. In this work, two decapeptides with fibrillar and globular morphologies were selected, blended with poly(ethylene oxide), and fabricated into composite mats via electrospinning.

Reversible Disulfide Bond Cross-Links as Tunable Levers of Phase Separation in Designer Biomolecular Condensates.

Biomolecular condensates (BCs) are membraneless hubs enriched with proteins and nucleic acids that have emerged as important players in many cellular functions. Uncovering the sequence determinants of proteins for phase separation is essential in understanding the biophysical and biochemical properties of BCs. Despite significant discoveries in the past decade, the role of cysteine residues in BC formation and dissolution has remained unknown.

Reversible disulfide bond crosslinks as tunable levers of phase separation in designer biomolecular condensates.

Biomolecular condensates (BCs) are membraneless hubs enriched in proteins and nucleic acids that have become important players in many cellular functions. Uncovering the sequence determinants of proteins for phase separation is important in understanding the biophysical and biochemical properties of BCs. Despite significant discoveries in the last decade, the role of cysteine residues in BC formation and dissolution has remained unknown.

Hybrid Bonding Bottlebrush Polymers Grafted from a Supramolecular Polymer Backbone.

Bottlebrush polymers, macromolecules consisting of dense polymer side chains grafted from a central polymer backbone, have unique properties resulting from this well-defined molecular architecture. With the advent of controlled radical polymerization techniques, access to these architectures has become more readily available. However, synthetic challenges remain, including the need for intermediate purification, the use of toxic solvents, and challenges with achieving long bottlebrush architectures due to backbone entanglements.

Single-cell coating with biomimetic extracellular nanofiber matrices.

Cell therapies offer great promise in the treatment of diseases and tissue regeneration, but their clinical use has many challenges including survival, optimal performance in their intended function, or localization at sites where they are needed for effective outcomes. We report here on a method to coat a biodegradable matrix of biomimetic nanofibers on single cells that could have specific functions ranging from cell signaling to targeting and helping cells survive when used for therapies. The fibers are composed of peptide amphiphile (PA) molecules that self-assemble into supramolecular nanoscale filaments.

CLIP-Seq analysis enables the design of protective ribosomal RNA bait oligonucleotides against ALS/FTD poly-GR pathophysiology.

Amyotrophic lateral sclerosis and frontotemporal dementia patients with a hexanucleotide repeat expansion in (C9-HRE) accumulate poly-GR and poly-PR aggregates. The pathogenicity of these arginine-rich dipeptide repeats (R-DPRs) is thought to be driven by their propensity to bind low-complexity domains of multivalent proteins. However, the ability of R-DPRs to bind native RNA and the significance of this interaction remain unclear.

amyloid peptides with subtle sequence variations differ in their self-assembly and nanomechanical properties.

Proteinaceous amyloids are well known for their widespread pathological roles but lately have emerged also as key components in several biological functions. The remarkable ability of amyloid fibers to form tightly packed conformations in a cross β-sheet arrangement manifests in their robust enzymatic and structural stabilities. These characteristics of amyloids make them attractive for designing proteinaceous biomaterials for various biomedical and pharmaceutical applications.

Role of supramolecular polymers in photo-actuation of spiropyran hydrogels.

Supramolecular-covalent hybrid polymers have been shown to be interesting systems to generate robotic functions in soft materials in response to external stimuli. In recent work supramolecular components were found to enhance the speed of reversible bending deformations and locomotion when exposed to light. The role of morphology in the supramolecular phases integrated into these hybrid materials remains unclear.

Supramolecular Nanofibers Block SARS-CoV-2 Entry into Human Host Cells.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection relies on its spike protein binding to angiotensin-converting enzyme 2 (ACE2) on host cells to initiate cellular entry. Blocking the interactions between the spike protein and ACE2 offers promising therapeutic opportunities to prevent infection. We report here on peptide amphiphile supramolecular nanofibers that display a sequence from ACE2 in order to promote interactions with the SARS-CoV-2 spike receptor binding domain.

Topical application of an irreversible small molecule inhibitor of lysyl oxidases ameliorates skin scarring and fibrosis.

Scarring is a lifelong consequence of skin injury, with scar stiffness and poor appearance presenting physical and psychological barriers to a return to normal life. Lysyl oxidases are a family of enzymes that play a critical role in scar formation and maintenance. Lysyl oxidases stabilize the main component of scar tissue, collagen, and drive scar stiffness and appearance.

A Perspective on the History and Current Opportunities of Aqueous RAFT Polymerization.

Reversible addition-fragmentation chain transfer (RAFT) polymerization has proven itself as a powerful polymerization technique affording facile control of molecular weight, molecular weight distribution, architecture, and chain end groups - while maintaining a high level of tolerance for solvent and monomer functional groups. RAFT is highly suited to water as a polymerization solvent, with aqueous RAFT now utilized for applications such as controlled synthesis of ultra-high molecular weight polymers, polymerization induced self-assembly, and biocompatible polymerizations, among others. Water as a solvent represents a non-toxic, cheap, and environmentally friendly alternative to organic solvents traditionally utilized for polymerizations.

Peptide Amphiphile Supramolecular Nanofibers Designed to Target Abdominal Aortic Aneurysms.

An abdominal aortic aneurysm (AAA) is a localized dilation of the aorta located in the abdomen that poses a severe risk of death when ruptured. The cause of AAA is not fully understood, but degradation of medial elastin due to elastolytic matrix metalloproteinases is a key step leading to aortic dilation. Current therapeutic interventions are limited to surgical repair to prevent catastrophic rupture.

Self-Assembled Peptide Amphiphile Nanofibers for Controlled Therapeutic Delivery to the Atherosclerotic Niche.

Atherosclerotic plaque remains the leading contributor to cardiovascular disease and requires invasive surgical procedures for its removal. Nanomedicine offers a minimally invasive approach to alleviate plaque burden by targeted therapeutic delivery. However, nanocarriers are limited without the ability to sense and respond to the diseased microenvironment.

Enhanced Detection of Desmoplasia by Targeted Delivery of Iron Oxide Nanoparticles to the Tumour-Specific Extracellular Matrix.

Diagnostic imaging of aggressive cancer with a high stroma content may benefit from the use of imaging contrast agents targeted with peptides that have high binding affinity to the extracellular matrix (ECM). In this study, we report the use of superparamagnetic iron-oxide nanoparticles (IO-NP) conjugated to a nonapeptide, CSGRRSSKC (CSG), which specifically binds to the laminin-nidogen-1 complex in tumours. We show that CSG-IO-NP accumulate in tumours, predominantly in the tumour ECM, following intravenous injection into a murine model of pancreatic neuroendocrine tumour (PNET).

Intravenous Delivery of Lung-Targeted Nanofibers for Pulmonary Hypertension in Mice.

Pulmonary hypertension is a highly morbid disease with no cure. Available treatments are limited by systemic adverse effects due to non-specific biodistribution. Self-assembled peptide amphiphile (PA) nanofibers are biocompatible nanomaterials that can be modified to recognize specific biological markers to provide targeted drug delivery and reduce off-target toxicity.

Development of novel nanofibers targeted to smoke-injured lungs.

Unlabelled: Smoke inhalation injury is associated with significant mortality and current therapies remain supportive. The purpose of our study was to identify proteins upregulated in the lung after smoke inhalation injury and develop peptide amphiphile nanofibers that target these proteins. We hypothesize that nanofibers targeted to angiotensin-converting enzyme or receptor for advanced glycation end products will localize to smoke-injured lungs.