Self-Assembled Peptide-Derived Proteolysis-Targeting Chimera (PROTAC) Nanoparticles for Tumor-Targeted and Durable PD-L1 Degradation in Cancer Immunotherapy.

Proteolysis-targeting chimeras (PROTACs) are a promising technique for the specific and durable degradation of cancer-related proteins via the ubiquitin-proteasome system in cancer treatment. However, the therapeutic efficacy of PROTACs is restricted due to their hydrophobicity, poor cell permeability and insufficient tumor-targeting ability. Herein, we develop the self-assembled peptide-derived PROTAC nanoparticles (PT-NPs) for precise and durable programmed death-ligand 1 (PD-L1) degradation in targeted tumors.

Assembly-Driven Oxidative Degradation of Melarsomine Triggered by Cyanuric Acid.

Molecular self-assembly can trigger or regulate specific chemical reactions that would otherwise be infeasible when molecules exist individually. Supramolecular structures can significantly affect the rate of chemical reactions; therefore, optimizing supramolecular structures by manipulating intermolecular interactions is crucial for achieving the desired reactivity. Melamine is known to form hydrogen bonds with cyanuric acid, resulting in the formation of a supramolecular network.

Mucoadhesive Mesalamine Prodrug Nanoassemblies to Target Intestinal Macrophages for the Treatment of Inflammatory Bowel Disease.

While mesalamine, a 5-aminosalicylic acid (5-ASA), is pivotal in the management of inflammatory bowel disease (IBD) through both step-up and top-down approaches in clinical settings, its widespread utilization is limited by low bioavailability at the desired site of action due to rapid and extensive absorption in the upper gastrointestinal (GI) tract. Addressing mesalamine's pharmacokinetic challenges, here, we introduce nanoassemblies composed exclusively of a mesalamine prodrug that pairs 5-ASA with a mucoadhesive and cathepsin B-cleavable peptide. In an IBD model, orally administered nanoassemblies demonstrate enhanced accumulation and sustained retention in the GI tract due to their mucoadhesive properties and the epithelial enhanced permeability and retention (eEPR) effect.

Aortic Angiosarcoma Manifesting as Multiple Musculoskeletal Metastases: A Case Report.

Aortic angiosarcomas are rare. Due to its rarity and metastatic presentation, it is difficult to diagnose metastatic aortic angiosarcoma. We describe the clinicopathological and radiologic features of a metastatic aortic angiosarcoma presenting as musculoskeletal metastases.

Effect of loading density and weather conditions on animal welfare and meat quality of slaughter pigs.

There are several factors that affect the welfare and meat quality of pigs during pre-slaughter transport. Among various factors, the effects of weather conditions and loading density were studied. A total of 3,726 finishing pigs were allotted to one of nine groups arranged in a 3 × 3 factorial design according to the weather conditions (low temperature [LT], under 10°C; normal temperature [NT], 10°C-24°C; high temperature [HT], upper 24°C), and loading density (low density [LD], upper 0.

Photonic control of ligand nanospacing in self-assembly regulates stem cell fate.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo self-assembly composed of azobenzene derivatives (Azo) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces -Azo-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly.

Self-Assembled Tamoxifen-Selective Fluorescent Nanomaterials Driven by Molecular Structural Similarity.

Most supramolecular systems were discovered by using a trial-and-error approach, leading to numerous synthetic efforts to obtain optimal supramolecular building blocks for selective guest encapsulation. Here, we report a simple coassembly strategy for preparing tamoxifen-selective supramolecular nanomaterials in an aqueous solution. The synthetic amphiphile molecule, 1,1,2,2-tetraphenylethylene (TPE), promotes large tamoxifen aggregate disassembly into smaller, discrete aggregates such as ribbon-like and micellar assemblies in coassembled solutions, enhancing the solubility and dispersion.

Modulating the folding and binding of peptides using a stimuli-responsive molecular tweezer.

This study presents the development of a β-hairpin (tryptophan zipper, Trpzip)-based molecular tweezer (MT) that can control the folding and binding of α-helical peptides. When an α-helix isolated from the p53 protein was conjugated with Trpzip in an optimized macrocyclic structure, the folded β-hairpin stabilized the helix conformation through the side chain-to-side chain stapling strategy, which notably enhanced target (hDM2) affinity of the peptide. On the other hand, the helicity and binding affinity were significantly reduced when the hairpin was unfolded by a redox stimulus.

Peptide Assembly of Different Dimensions and Their Effect on Myoblast Proliferation.

Variations in the functionalities of materials of different dimensions containing the same functional groups can be attributed to the structural stability and morphology of the materials. The morphology of peptide assemblies can influence their interactions with biological systems and ultimately modulate their bioactivity. Among reported Arg-Gly-Asp (RGD)-based supramolecular materials, two-dimensional (2-D) peptide assembly has been rarely studied.

Reduction-Responsive Supramolecular Sheets for Selective Regulation of Facultative Anaerobe Agglutination.

Stimuli-responsive supramolecular materials have promising biological applications because of their ability to rapidly undergo significant structural changes in response to diverse stimuli. Herein, supramolecular sheets assembled via charge-transfer interactions between the pyrene moiety of a d-mannose-containing amphiphile and 7,7,8,8-tetracyanoquinodimethane (TCNQ) are reported. The supramolecular sheets show reduction-responsive behavior, in which their disassembly is triggered by the reduction of TCNQ by sodium sulfide.

Effects of supplemental different clay minerals in broiler chickens under cyclic heat stress.

The objective of this study was to investigate the effect of supplementing clay minerals and organic chromium in feed on broiler chicken under heat stress (HS). A total of 90 one-day-old broiler chicken (Arbor Acres) with an initial body weight of 45.0 ± 0.

Two-Dimensional Peptide Assembly Arene-Perfluoroarene Interactions for Proliferation and Differentiation of Myoblasts.

Supramolecular assembly based on aromatic interactions can provide well-defined nanostructures with an understanding of intermolecular interactions at the molecular level. The peptide assembly a supramolecular approach can overcome the inherent limitations of bioactive peptides, such as proteolytic degradations and rapid internalizations into the cytosol. Although extensive research has been carried out on supramolecular peptide materials with a two-dimensional (2D) structure, more needs to be reported on biological activity studies using well-defined 2D peptide materials.

Tumor-Specific Monomethyl Auristatin E (MMAE) Prodrug Nanoparticles for Safe and Effective Chemotherapy.

A prodrug is bioreversible medication that is specifically converted to the active drugs by enzymes overexpressed in the tumor microenvironment, which can considerably reduce the chemotherapy-induced side effects. However, prodrug strategies usually have low antitumor efficacy compared to free drugs by delayed drug release. This is because they need time to be activated by enzymatic cleavage and they also cannot be fully recovered to the active drugs.

Photoswitchable Microgels for Dynamic Macrophage Modulation.

Dynamic manipulation of supramolecular self-assembled structures is achieved irreversibly or under non-physiological conditions, thereby limiting their biomedical, environmental, and catalysis applicability. In this study, microgels composed of azobenzene derivatives stacked via π-cation and π-π interactions are developed that are electrostatically stabilized with Arg-Gly-Asp (RGD)-bearing anionic polymers. Lateral swelling of RGD-bearing microgels occurs via cis-azobenzene formation mediated by near-infrared-light-upconverted ultraviolet light, which disrupts intermolecular interactions on the visible-light-absorbing upconversion-nanoparticle-coated materials.

Recognition of 3D Chiral Microenvironments for Myoblast Differentiation.

Cell chirality plays a critical role in the linkage between molecular chirality and the asymmetrical biological functions of body organs. However, enantioselective interactions between cell chirality and the extracellular environment are not yet fully understood. In this study, we investigated the effects of structurally chiral extracellular microenvironments on cellular alignments and differentiations.

Comparative study of cathepsin B-cleavable linkers for the optimal design of cathepsin B-specific doxorubicin prodrug nanoparticles for targeted cancer therapy.

A carrier-free prodrug nanoparticle has emerged as a potential approach to cancer therapy. It plays a vital role in enhancing the tumor targeting and therapeutic efficacy of the anticancer agent at sites of intention wherein the prodrug nanoparticle is potentially activated. Herein, five derivatives of cathepsin B-cleavable prodrugs are synthesized via chemically conjugating different cathepsin B-cleavable peptides (Phe-Arg-Arg-Gly, Phe-Arg-Arg-Leu, Phe-Arg-Arg-Leu-Gly, Phe-Leu-Arg-Arg-Gly) to doxorubicin (DOX).

Transformation of Supramolecular Membranes to Vesicles Driven by Spontaneous Gradual Deprotonation on Membrane Surfaces.

The various proteins and asymmetric lipid bilayers present in cell membranes form curvatures, resulting in structural transformations to generate vesicles. Fission and fusion processes between vesicles and cell membranes are reversible in living organisms. Although the transformation of a two-dimensional membrane to a three-dimensional vesicle structure is a common natural phenomenon, the lack of a detailed understanding at the molecular level limits the development of synthetic systems for functional materials.

Stimbiotic Supplementation Alleviates Poor Performance and Gut Integrity in Weaned Piglets Induced by Challenge with .

The aim of this study was to investigate the effects of stimbiotic (STB), a xylanase and xylo-oligosaccharide complex. A total of 36 male weaned pigs with initial body weights of 8.49 ± 0.

Selective Anticancer Materials by Self-Assembly of Synthetic Amphiphiles Based on -Acetylneuraminic Acid.

-Acetylneuraminic acid (Neu5Ac), one of the abundant types of sialic acid, is an emerging anticancer agent owing to its ability to target selectins in the plasma membrane of cancer cells. Considering the functionality of Neu5Ac, obtaining novel Neu5Ac-conjugated materials with a selective and an enhanced antitumor activity has remained a challenge. Herein, we report the supramolecular materials of three novel amphiphiles composed of Neu5Ac as a hydrophilic segment and pyrene or adamantane as a hydrophobic segment.

Anti-PD-L1 peptide-conjugated prodrug nanoparticles for targeted cancer immunotherapy combining PD-L1 blockade with immunogenic cell death.

Cancer immunotherapy combining immune checkpoint blockade (ICB) with chemotherapeutic drugs has provided significant clinical advances. However, such combination therapeutic regimen has suffered from severe toxicity of both drugs and low response rate of patients. In this study, we propose anti-PD-L1 peptide-conjugated prodrug nanoparticles (PD-NPs) to overcome these obstacles of current cancer immunotherapy.

Supramolecular Two-Dimensional Systems and Their Biological Applications.

Various biological systems rely on the supramolecular assembly of biomolecules through noncovalent bonds for performing sophisticated functions. In particular, cell membranes, which are 2D structures in biological systems, have various characteristics such as a large surface, flexibility, and molecule-recognition ability. Supramolecular 2D materials based on biological systems provide a novel perspective for the development of functional 2D materials.