The immunoglobulin of yolk and cerium oxide-based fibrous poly(L-lactide-co-glycolide)/gelatin dressings enable skin regeneration in an infectious wound model.

The bacterial infection and oxidative wound microenvironment delay skin repair and necessitate intelligent wound dressings to enable scarless wound healing. The immunoglobulin of yolk (IgY) exhibits immunotherapeutic potential for the potential treatment of antimicrobial-resistant pathogens, while cerium oxide nanoparticles (CeO NPs) could scavenge superoxide dismutase (SOD) and inflammation. The overarching objective of this study was to incorporate IgY and CeO NPs into poly(L-lactide-co-glycolide)/gelatin (PLGA/Gel)-based dressings (P/G@IYCe) for infected skin repair.

Proposal for a non-adhesive single-cell culture technology for primary hepatocytes.

Unlabelled: Primary hepatocytes (PHs) are indispensable for studying liver function, drug screening, and regenerative medicine. However, freshly isolated PHs only survive for a few hours in non-adherent suspension culture. This study proposes treatment with PEG-GRGDS, a polymer-peptide conjugate comprising polyethylene glycol (PEG) and the pentapeptide sequence Gly-Arg-Gly-Asp-Ser (GRGDS), to sustain the viability of dispersed single PHs under non-adherent conditions.

Dynamic Correlation Analysis between Stress-Strain Curve and Polymer Film Structure Using Persistent Homology.

Coarse-grained molecular dynamics (CG-MD) simulations and subsequent persistent homology (PH) analysis were performed to correlate the structure and stress-strain behavior of polymer films. During uniaxial tensile MD simulations, the first principal component of the persistence diagram obtained by principal component analysis (PCA) was in good agreement with the stress-strain curve. This indicates that PH + PCA can identify critical ring structures relevant to the dynamic changes in MD simulations without requiring any prior knowledge.

Poly(vinyl alcohol) potentiating an inert d-amino acid-based drug for boron neutron capture therapy.

Since the discovery of d-amino acids, they have been considered inactive and have not been used as potent drugs. Here, we report that simple mixing with poly(vinyl alcohol) (PVA) unleashed latent potentials of d-amino acids in boron neutron capture therapy (BNCT). PVA formed boronate esters with seemingly useless boronated d-amino acids and induced tumor-associated amino acid transporter-superselective internalization and prolonged intracellular retention, accomplishing complete cure of tumors.

Synthesis and Optimization of Ethylenediamine-Based Zwitterion on Polymer Side Chain for Recognizing Narrow Tumorous pH Windows.

Polyzwitterions that show the alternation of net charge in response to external stimuli have attracted great attention as a new class of surface-polymers on nanomedicines. However, the correlation between their detailed molecular structures and expression of antifouling properties under physiological condition remain controversial. Herein, we synthesized a series of ethylenediamine-based polyzwitterions with carboxy groups/sulfonic groups and ethylene, propylene, and butylene spacers as potential surface-polymers for nanomedicines, allowing sensitive recognition of tumor acidic environments (pH = 6.

Fine-tuning the cytotoxicity profile of N,N,N-trimethyl chitosan through trimethylation, molecular weight, and polyelectrolyte complex nanoparticles.

N,N,N-trimethyl chitosan (TMC) is a promising biopolymer for pharmaceutical applications due to its enhanced solubility and bioadhesive properties, though its cytotoxic limitations necessitate careful modification to ensure safety and efficacy. This study sought to investigate whether nanoparticle (NP) formation could reduce the anticipated cytotoxic effects of TMC, thus improving its applicability across a wider spectrum of pharmaceutical uses. TMC's capability to form NPs with anionic polyelectrolytes led to the application of chondroitin sulfate (ChS) in this study.

Nanoenabled IL-15 Superagonist via Conditionally Stabilized Protein-Protein Interactions Eradicates Solid Tumors by Precise Immunomodulation.

Protein complexes are crucial structures that control many biological processes. Harnessing these structures could be valuable for therapeutic therapy. However, their instability and short lifespans need to be addressed for effective use.

Master Regulators of Causal Networks in Intestinal- and Diffuse-Type Gastric Cancer and the Relation to the RNA Virus Infection Pathway.

Causal networks are important for understanding disease signaling alterations. To reveal the network pathways affected in the epithelial-mesenchymal transition (EMT) and cancer stem cells (CSCs), which are related to the poor prognosis of cancer, the molecular networks and gene expression in diffuse- and intestinal-type gastric cancer (GC) were analyzed. The network pathways in GC were analyzed using Ingenuity Pathway Analysis (IPA).

Polymer-drug and polymer-protein conjugated nanocarriers: Design, drug delivery, imaging, therapy, and clinical applications.

Polymer-drug conjugates and polymer-protein conjugates have been pivotal in the realm of drug delivery systems for over half a century. These polymeric drugs are characterized by the conjugation of therapeutic molecules or functional moieties to polymers, enabling a range of benefits including extended circulation times, targeted delivery, controlled release, and decreased immunogenicity. This review delves into recent advancements and challenges in the clinical translations and preclinical studies of polymer-drug conjugates and polymer-protein conjugates.

Triphenylphosphonium-modified catiomers enhance mRNA delivery through stabilized polyion complexation.

Nanocarriers based on cationic materials play a central role in the success of mRNA-based therapies. Traditionally, amine-bearing lipids and polymers have been successfully employed for creating mRNA-loaded nanocarriers, though they still present challenges, such as physical and biological instability, limiting both delivery efficiency and therapeutic potential. Non-amine cations could be a promising avenue in addressing these limitations.

Mesoporous Silicon with Strontium-Powered Poly(Lactic-Co-Glycolic acid)/Gelatin-Based Dressings Facilitate Skin Tissue Repair.

Purpose: Functional inorganic nanomaterials (NMs) are widely exploited as bioactive materials and drug depots. The lack of a stable form of application of NMs at the site of skin injury, may impede the removal of the debridement, elevate pH, induce tissue toxicity, and limit their use in skin repair. This necessitates the advent of innovative wound dressings that overcome the above limitations.

Droplet Microfluidics Powered Hydrogel Microparticles for Stem Cell-Mediated Biomedical Applications.

Stem cell-related therapeutic technologies have garnered significant attention of the research community for their multi-faceted applications. To promote the therapeutic effects of stem cells, the strategies for cell microencapsulation in hydrogel microparticles have been widely explored, as the hydrogel microparticles have the potential to facilitate oxygen diffusion and nutrient transport alongside their ability to promote crucial cell-cell and cell-matrix interactions. Despite their significant promise, there is an acute shortage of automated, standardized, and reproducible platforms to further stem cell-related research.

Composite superplastic aerogel scaffolds containing dopamine and bioactive glass-based fibers for skin and bone tissue regeneration.

Multifunctional bioactive biomaterials with integrated bone and soft tissue regenerability hold great promise for the regeneration of trauma-affected skin and bone defects. The aim of this research was to fabricate aerogel scaffolds (GD-BF) by blending the appropriate proportions of short bioactive glass fiber (BGF), gelatin (Gel), and dopamine (DA). Electrospun polyvinyl pyrrolidone (PVP)-BGF fibers were converted into short BGF through calcination and homogenization.

Active control of pharmacokinetics using light-responsive polymer-drug conjugates for boron neutron capture therapy.

In boron neutron capture therapy (BNCT), boron drugs should exhibit high intratumoral boron concentrations during neutron irradiation, while being cleared from the blood and normal organs. However, it is usually challenging to achieve such tumor accumulation and quick clearance simultaneously in a temporally controlled manner. Here, we developed a polymer-drug conjugate that can actively control the clearance of the drugs from the blood.

Composite Aerogel Scaffolds Containing Flexible Silica Nanofiber and Tricalcium Phosphate Enable Skin Regeneration.

Poor hemostatic ability and less vascularization at the injury site could hinder wound healing as well as adversely affect the quality of life (QOL). An ideal wound dressing should exhibit certain characteristics: (a) good hemostatic ability, (b) rapid wound healing, and (c) skin appendage formation. This necessitates the advent of innovative dressings to facilitate skin regeneration.

Facile Generation of Heterotelechelic Poly(2-Oxazoline)s Towards Accelerated Exploration of Poly(2-Oxazoline)-Based Nanomedicine.

Controlling the end-groups of biocompatible polymers is crucial for enabling polymer-based therapeutics and nanomedicine. Typically, end-group diversification is a challenging and time-consuming endeavor, especially for polymers prepared via ionic polymerization mechanisms with limited functional group tolerance. In this study, we present a facile end-group diversification approach for poly(2-oxazoline)s (POx), enabling quick and reliable production of heterotelechelic polymers to facilitate POxylation.

Fine tuning of the net charge alternation of polyzwitterion surfaced lipid nanoparticles to enhance cellular uptake and membrane fusion potential.

Lipid nanoparticles (LNPs) coated with functional and biocompatible polymers have been widely used as carriers to deliver oligonucleotide and messenger RNA therapeutics to treat diseases. Poly(ethylene glycol) (PEG) is a representative material used for the surface coating, but the PEG surface-coated LNPs often have reduced cellular uptake efficiency and pharmacological activity. Here, we demonstrate the effect of pH-responsive ethylenediamine-based polycarboxybetaines with different molecular weights as an alternative structural component to PEG for the coating of LNPs.

Carrier-free mRNA vaccine induces robust immunity against SARS-CoV-2 in mice and non-human primates without systemic reactogenicity.

Carrier-free naked mRNA vaccines may reduce the reactogenicity associated with delivery carriers; however, their effectiveness against infectious diseases has been suboptimal. To boost efficacy, we targeted the skin layer rich in antigen-presenting cells (APCs) and utilized a jet injector. The jet injection efficiently introduced naked mRNA into skin cells, including APCs in mice.

Methacrylated gelatin and platelet-rich plasma based hydrogels promote regeneration of critical-sized bone defects.

Physiological repair of large-sized bone defects requires instructive scaffolds with appropriate mechanical properties, biocompatibility, biodegradability, vasculogenic ability and osteo-inductivity. The objective of this study was to fabricate injectable hydrogels using platelet-rich plasma (PRP)-loaded gelatin methacrylate (GM) and employ them for the regeneration of large-sized bone defects. We performed various biological assays as well as assessed the mechanical properties of GM@PRP hydrogels alongside evaluating the release kinetics of growth factors (GFs) from hydrogels.

Long noncoding RNA TUG1 promotes cisplatin resistance in ovarian cancer via upregulation of DNA polymerase eta.

Chemoresistance is a major cause of high mortality and poor survival in patients with ovarian cancer (OVCA). Understanding the mechanisms of chemoresistance is urgently required to develop effective therapeutic approaches to OVCA. Here, we show that expression of the long noncoding RNA, taurine upregulated gene 1 (TUG1), is markedly upregulated in samples from OVCA patients who developed resistance to primary platinum-based therapy.

mRNA vaccine designs for optimal adjuvanticity and delivery.

Adjuvanticity and delivery are crucial facets of mRNA vaccine design. In modern mRNA vaccines, adjuvant functions are integrated into mRNA vaccine nanoparticles, allowing the co-delivery of antigen mRNA and adjuvants in a unified, all-in-one formulation. In this formulation, many mRNA vaccines utilize the immunostimulating properties of mRNA and vaccine carrier components, including lipids and polymers, as adjuvants.

Selective Intracellular Delivery of Antibodies in Cancer Cells with Nanocarriers Sensing Endo/Lysosomal Enzymatic Activity.

The differential enzymatic activity in the endo/lysosomes of particular cells could trigger targeted endosomal escape functions, enabling selective intracellular protein delivery. However, this strategy may be jeopardized due to protein degradation during endosomal trafficking. Herein, using custom made fluorescent probes to assess the endosomal activity of cathepsin B (CTSB) and protein degradation, we found that certain cancer cells with hyperacidified endosomes grant a spatiotemporal window where CTSB activity surpass protein digestion.

Molecular Dynamics Simulation of Adhesion of Additive Molecules in Paint Materials toward Enhancement of Anticorrosion Performance.

Adsorption energies of additive molecules in paint materials on the iron oxide substrate are investigated by molecular dynamics (MD) simulations to find the key feature of adhesion, which is one of the indispensable elements for the corrosion resistance of coated materials. Both edge-on and face-on adsorptions are observed for most additive molecules such as phenylsuccinic acid and benzoic acid. On the other hand, only the edge-on adsorption is observed for the specific molecule having a benzothiazole ring due to the effect of steric conformation.

Ionizable Polymeric Micelles with Phenylalanine Moieties Enhance Intracellular Delivery of Self-Replicating RNA for Long-Lasting Protein Expression In Vivo.

mRNA-based therapeutics are revolutionizing the landscape of medical interventions. However, the short half-life of mRNA and transient protein expression often limits its therapeutic potential, demanding high treatment doses or repeated administrations. Self-replicating RNA (RepRNA)-based treatments could offer enhanced protein production and reduce the required dosage.