Journal of materials chemistry. B最新文献

Prolonged urinary catheterization often leads to two major complications, bacterial biofilm formation and fibrotic tissue development, both of which hinder catheter function. However, current catheter designs fail to address these challenges simultaneously. In this study, the surface of a polyvinyl chloride (PVC) catheter was conjugated with TetraF2W-RR, an antimicrobial peptide (AMP) effective against drug-resistant methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa (MDRPA) strains, and DR8, an antifibrotic peptide (AFP) that inhibits excessive extracellular matrix (ECM) buildup to provide both antimicrobial and antifibrotic effects. Covalently co-immobilizing TetraF2W-RR and DR8 peptides onto PVC surfaces (PVC-AMP/AFP) via cold atmospheric plasma (CAP) created dual-functional urinary catheters that prevent biofilm formation by MRSA and MDRPA while diminishing fibrotic responses in vitro. PVC-AMP/AFP surfaces demonstrated strong antibacterial and antibiofilm activity without harming NIH 3T3 cells. In a TGF-β1-stimulated fibroblast model, PVC-AMP/AFP catheter groups significantly reduced fibrotic gene expression (COL1A1, FN1, ACTA2, and TGF-β1), lowered total collagen levels, and decreased COL1A1 and α-SMA expression by immunofluorescence staining. A wound healing assay in a TGF-β1-induced fibrotic fibroblast model further confirmed suppressed fibroblast migration in PVC-AMP/AFP catheter groups. To the best of our knowledge, this is the first attempt to simultaneously impart antibacterial and antifibrotic functionalities to PVC urinary catheters via covalent co-immobilization of AMP and AFP. This combined approach offers a promising strategy to improve the long-term safety and efficacy of indwelling urinary catheters and could be applied to a variety of implantable biomaterials.

A substantial fraction of human proteins, including secreted and membrane-localized species, are linked to diseases such as cancer and neurodegeneration upon overexpression or misfolding. However, state-of-the-art targeted protein degradation (TPD) strategies targeting these proteins face limitations such as the "hook" effect and interference with normal cell function. Recently, we developed Protein-Radical-Oxidation Targeting Enediyne Chimeras (PROTECs), a TPD platform that employs an enediyne warhead to directly degrade target proteins without requiring cellular organelles for protein degradation. To extend the application scenarios of PROTECs to the extracellular environment, we herein designed Compound-1, a PROTEC molecule incorporating a PD-L1-targeting ligand (BMS-57), an intrinsic enediyne degradation warhead, and sulfate-based hydrophilicity-adjusting groups to enforce extracellular localization. Compound-1 induced potent and selective degradation of membrane PD-L1 in HeLa cells, achieving a half-maximal degradation concentration (DC₅₀) of 44 nM, independent of both proteasomal and lysosomal activity. Furthermore, the targeted PD-L1 degradation reversed tumor immune evasion and enhanced cancer cell killing by peripheral blood mononuclear cells. This study establishes the PROTEC platform as a robust and modular strategy for degrading membrane-associated and extracellular disease-relevant proteins.

Liquid multisensors are in high demand due to their wide range of applications. Recent advances in electronics allow an integration of several individual devices for target and control measurements on one chip. We studied aptamer-modified electrolyte-gated field-effect transistors (EGOFETs) as basic sensor elements for single-chip multitarget detection. We used an aptamer with a pH-dependent conformational switch as a model recognition element allowing application of the EGOFET as a single element for detecting three targets of different nature. The fabricated EGOFET device has been shown to be sensitive to the conformation of the aptamer. The sensor is sensitive to the pH changes in the range of pH 6-8 due to the H⁺-dependent assembly of an i-motif DNA structure. Under the i-motif-unfavorable conditions (pH ≥ 7.3), the unfolded cytosine loop forms a complex with Ag⁺ ions providing a new conformation. Finally, under the i-motif-favorable conditions (pH < 7.3), the folded i-motif binds to influenza A virus. The EGOFET signals for these three analytes lie in different ranges allowing their clear discrimination. Applicability of the designed device under biologically relevant conditions was proved for biological fluids such as saliva and plasma with a viral load typical for patients with influenza. The proof-of-concept for single-chip multitarget detection based on EGOFETs with one recognition element is implemented for the first time. This example of the model recognition element with combined properties integrated into the EGOFET paves the way to managing the properties of the EGOFET-based biosensors and, in the future, to developing single-chip multisensors on the EGOFET platform.

Self-assembling phage-inspired carriers based on macrocyclic molecules have the potential to overcome antibiotic resistance and extend the antimicrobial effect of drugs. In this study, we have synthesized a new water-soluble pillar[5]arene containing thioglycoside fragments. This compound had an affinity for a model lipid membrane, underwent self-assembly, and associated with the fluoroquinolone antibiotic ciprofloxacin hydrochloride (Cipro) to form biocompatible supramolecular nanostructures. UV-vis and fluorescence spectroscopies were used to assess the ability of the pillar[5]arene/antibiotic system to form supramolecular complexes in a 1 : 2 stoichiometry (lg K_1 : 1 = 1.49 and lg K_1 : 2 = 4.22). Dynamic light scattering (DLS) and transmission electron microscopy (TEM) studies confirmed the formation of stable pillararene/antibacterial complexes with particle sizes in the range of 250-300 nanometers. And the biological characteristics of the systems we obtained indicate their low toxicity to cancer (A549) and normal cells (LEK and HSF), with a twofold increase in the inhibitory effect of the combined pillar[5]arene/antibiotic system on the strain of K. pneumoniae with increased resistance to ciprofloxacin. The improved antibacterial properties of the antibiotic in combination with the pillar[5]arene may be due to the blocking of efflux pumps, which is confirmed by molecular docking.

Correction for 'Surface nanocrystallization enhances the biomedical performance of additively manufactured stainless steel' by Sumit Ghosh et al., J. Mater. Chem. B, 2023, 11, 9697-9711, https://doi.org/10.1039/D3TB01534C.

Waterborne bacterial contamination remains a pressing global health concern, demanding point-of-care (POC) devices for rapid and efficient on-site detection. High costs, long processing times and reliance on sophisticated equipment limit conventional methods. Thus, this study proposes the fabrication of a low-cost, disposable paper-based electrochemical biosensor for the effective and selective detection of Gram-negative bacteria. The developed biosensor was modified with a g-C₃N₄/amine-functionalised carbon dot composite to boost signal transduction and offer stable immobilisation of a TLR-4/MD-2 bioreceptor, which detects explicitly the lipopolysaccharide layer of Gram-negative bacterial samples. The developed paper-based biosensor showed excellent analytical performance with remarkable specificity and achieved a low theoretical limit of detection of 0.66 CFU mL^-1 and 0.88 CFU mL^-1 for E. coli and P. aeruginosa, respectively, across a wide dynamic range of 1.5 to 1.5 × 10⁵ CFU mL^-1. Furthermore, the biosensor demonstrated good stability, reproducibility and ability to attain a satisfactory low LOD in the spiked tap and pond water samples. Moreover, the simple disposability of the paper electrodes lowers the cross-contamination issues and ensures the safety of the environment. Collectively, this work introduces a sustainable, low-cost, and portable biosensing platform that effectively integrates a nanomaterial for enhanced transduction with receptor-based specificity, offering significant potential for early diagnosis of waterborne bacterial contamination and advancing public health protection through POC applications.

Photocleavable protective groups (PPGs) offer a straightforward method of temporarily masking the aggressive functions of organic compounds and inactivating biologically active or toxic substrates. The active species can then be released from their photoactivatable precursors in a controlled manner upon exposure to light. In this study, we present a series of photocages based on the novel fluorescent scaffold 2-aryl-2H-1,2,3-triazol-4-yl-thiazoles (ATTs), incorporating proteinogenic amino acids, the biologically active compound biotin, the anticancer agent melphalan, and model compounds such as aromatic acids. Studies of photodegradation under various conditions using mass spectrometry, spectral and kinetic analyses, and quantum mechanical calculations have shown that acid release from the photoconjugates (ATT-PCs) depends on fluorophore fragment structure, acid nature, and the presence of air, water or a phosphate buffer solution (pH of 7.4), as well as the light source power and λ_ir. The release of acid during photodissociation was confirmed through high-resolution mass spectrometry and biological experiments, including the MTT assay and the imaging of Vero cells incubated with ATT-PCs, utilising a confocal scanning microscope. The photorelease mechanism was explored using both experimental studies and quantum mechanical calculations, which revealed that the properties and reactivity of this photosystem are predominantly influenced by the transition to the triplet state. Additionally, the findings indicated that ATT-PCs effectively absorb light in the visible spectrum and exhibit intense fluorescence, even in a DMSO-PBS mixture at a 1 : 9 ratio. Furthermore, ATT-PCs can function as photosensitisers, capable of generating reactive oxygen species (ROS). Cell studies demonstrate the rapid intracellular uptake of ATT-PCs by Vero cells, with accumulation in the endoplasmic reticulum (ER) or lipid droplets within a 0.5-hour incubation period.

Targeted modulation of enzyme activity offers a promising strategy for both elucidating catalytic mechanisms and developing novel therapeutics. In this study Zn²⁺ ions were introduced as an effective competitive inhibitor of fumarase, a pivotal enzyme in the citric acid cycle. Zn²⁺ binding significantly alters the Michaelis constant (K_m) for both L-malate and fumarate, with a pronounced preference for inhibiting the reverse reaction (L-malate to fumarate), a direction relevant to redox homeostasis and anaplerotic flux. A major limitation of the clinical application of many metal-based inhibitors is their poor water solubility. To overcome this challenge and introduce a new class of enzyme inhibitors, zinc-modified carbon quantum dots (Zn-CQDs) were synthesized. Owing to their polar surface, Zn-CQDs interact more effectively with the enzyme, which increases the local concentration of Zn²⁺ ions at the active site. As a result, these nanomaterials exhibit enhanced water solubility and significantly greater inhibitory potency compared to free Zn²⁺ ions. Biophysical and kinetic analyses confirmed the competitive inhibition mechanism and demonstrated that Zn-CQDs interact with the enzyme without perturbing its secondary structure. Notably, both Zn²⁺ ions and Zn-CQDs preferentially inhibited the reverse reaction of fumarase, offering precise control over fumarase activity. Molecular docking and MD simulations elucidated the plausible binding site of Zn²⁺ within the active site. It was found that Zn²⁺ interacts with Glu340, a residue previously shown to be involved in binding fumarase inhibitors. These findings establish Zn-CQDs as a novel class of water-soluble fumarase inhibitors, distinguished by their facile synthesis, tunable solubility, and selective inhibition profile. This work highlights the potential of zinc-based nanomaterials in enzyme regulation, offering a powerful alternative to existing inhibitors and developing targeted redox-sensitive therapeutic strategies.

Heart disease has become a major threat to global health. In recent years, extracellular vesicles (EVs) have become a research hotspot in heart regeneration and repair due to their unique intercellular communication function and advantages in cell-free therapy. This paper systematically summarizes the sources, characteristics, engineering, and clinical applications of EVs in heart regeneration. Cardiac therapy-related EVs significantly reduce cardiac fibrosis, regulate inflammation and immunity, improve the myocardial microenvironment, and promote angiogenesis by delivering biologically active molecules such as proteins, lipids, and microRNAs. In addition, bioengineering techniques (such as targeted peptide modification and hydrogel delivery systems) have further improved the cardiac targeting and long-lasting efficacy of specific EVs. The above methods have shown high repair potential in disease models such as cardiac ischemia-reperfusion injury, myocardial infarction, heart failure, and structural heart diseases. However, the clinical application of EVs still faces some challenges that need to be urgently addressed. Future research needs to focus on standardized and scaled production processes, long-lasting storage capacity, and precise and specific mechanisms of action of EVs to facilitate the translation of EVs from basic research to the clinic.

Oral squamous cell carcinoma (OSCC) remains a challenging malignancy with high recurrence and metastasis rates, often limited by insufficient immunogenicity and a suppressive tumor microenvironment. Immunogenic cell death (ICD) offers a promising approach to convert cell death into antitumor immunity; yet, its efficacy depends on precise modulation of autophagy and endoplasmic reticulum stress (ERS). Here, we report that combining the BET inhibitor JQ1 with the autophagy inhibitor chloroquine (CQ) synergistically amplifies ERS, leading to enhanced ICD in OSCC models. This combination promotes robust damage-associated molecular pattern (DAMP) release, dendritic cell activation, and antigen-specific CD8⁺ T-cell responses. To enable localized and efficient delivery, we engineered self-assembled JQ1/CQ nanoparticles stabilized through π-π stacking and integrated them into dissolvable cryomicroneedles. This minimally invasive platform ensures sustained drug release, improves tumor accumulation, and minimizes systemic exposure. Our study not only elucidates a druggable autophagy-ERS-ICD axis but also provides a versatile transdermal delivery strategy with potential applicability to a range of solid tumors.