Unlocking the potential: phenylboronic acid as a nuclear-targeting boron agent for neutron capture therapy.

It has been proposed that boron neutron capture therapy (BNCT) holds promise as a treatment modality for melanoma. However, the effectiveness of boron agents in delivery remains a critical issue to be addressed for BNCT. To this end, phenylboronic acid, which exhibits good water solubility and low cytotoxicity similar to BPA, has been investigated as a potential nuclear-targeting boron agent. The boron concentration of phenylboronic acid was found to be 74.47 ± 12.17 ng/106 B16F10 cells and 45.77 ± 5.64 ng/106 cells in the nuclei. Molecular docking experiments were conducted to investigate the binding of phenylboronic acid to importin proteins involved in nuclear transport. The potential of phenylboronic acid to serve as a desirable nucleus-delivery boron agent for neutron capture therapy in melanoma warrants further exploration.

Antibacterial and antibiofilm activity of halogenated phenylboronic acids against Vibrio parahaemolyticus and Vibrio harveyi.

Vibrios are associated with live seafood because they are part of the indigenous marine microflora. In Asia, foodborne infections caused by Vibrio spp. are common. In recent years, V. parahaemolyticus has become the leading cause of all reported food poisoning outbreaks. Therefore, the halogenated acid and its 33 derivatives were investigated for their antibacterial efficacy against V. parahaemolyticus. The compounds 3,5-diiodo-2-methoxyphenylboronic acid (DIMPBA) and 2-fluoro-5-iodophenylboronic acid (FIPBA) exhibited antibacterial and antibiofilm activity. DIMPBA and FIPBA had minimum inhibitory concentrations of 100 µg/mL for the planktonic cell growth and prevented biofilm formation in a dose-dependent manner. Both iodo-boric acids could diminish the several virulence factors influencing the motility, agglutination of fimbria, hydrophobicity, and indole synthesis. Consequently, these two active halogenated acids hampered the proliferation of the planktonic and biofilm cells. Moreover, these compounds have the potential to effectively inhibit the presence of biofilm formation on the surface of both squid and shrimp models.

The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis.

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

In vitro activity of ceftazidime/avibactam, cefiderocol, meropenem/vaborbactam and imipenem/relebactam against clinical strains of the Stenotrophomonas maltophilia complex.

BACKGROUND: Infections caused by Stenotrophomonas maltophilia and related species are increasing worldwide. Unfortunately, treatment options are limited, whereas the antimicrobial resistance is increasing. METHODS: We included clinical isolates identified as S. maltophilia by VITEK 2 Compact. Ceftazidime/avibactam, meropenem/vaborbactam, imipenem/relebactam, cefiderocol, quinolones, and tetracycline family members were evaluated by broth microdilution method and compared with first-line treatment drugs. Minimum inhibitory concentrations (MICs) were reported for all antibiotics. We sequenced the Whole Genome of cefiderocol resistant strains (CRSs) and annotated their genes associated with cefiderocol resistance (GACR). Presumptive phylogenetic identification employing the 16S marker was performed. RESULTS: One hundred and one clinical strains were evaluated, sulfamethoxazole and trimethoprim, levofloxacin and minocycline showed susceptibilities of 99.01%, 95.04% and 100% respectively. Ceftazidime was the antibiotic with the highest percentage of resistance in all samples (77.22%). Five strains were resistant to cefiderocol exhibiting MIC values ≥ 2 µg/mL (4.95%). The ß-lactamase inhibitors meropenem/vaborbactam and imipenem/relebactam, failed to inhibit S. maltophilia, preserving both MIC50 and MIC90 ≥64 µg/mL. Ceftazidime/avibactam restored the activity of ceftazidime decreasing the MIC range. Tigecycline had the lowest MIC range, MIC50 and MIC90. Phylogeny based on 16S rRNA allowed to identify to cefiderocol resistant strains as putative species clustered into Stenotrophomonas maltophilia complex (Smc). In these strains, we detected GARCs such as Mutiple Drug Resistance (MDR) efflux pumps, L1-type ß-lactamases, iron transporters and type-1 fimbriae. CONCLUSION: Antimicrobial resistance to first-line treatment is low. The in vitro activity of new ß-lactamase inhibitors against S. maltophilia is poor, but avibactam may be a potential option. Cefiderocol could be considered as a potential new option for multidrug resistant infections. Tetracyclines had the best in vitro activity of all antibiotics evaluated.

A comparative study of electropolymerization and photopolymerization for the determination of molnupiravir and their application in an electrochemical sensor via computationally designed molecularly imprinted polymers.

A comparative analysis of molecularly imprinted polymers based on different synthesis techniques was performed for the recognition of molnupiravir (MOL). The polymerizations were performed with 3-thienyl boronic acid (3-TBA) as a functional monomer by electropolymerization (EP) and with guanine methacrylate (GuaM) as a functional monomer by photopolymerization (PP). Morphological and electrochemical characterizations of the developed sensors were investigated to verify the constructed sensors. Moreover, quantum chemical calculations were used to evaluate changes on the electrode surface at the molecular and electronic levels. The dynamic linear range of both designed sensors under optimized experimental conditions was found to be 7.5 × 10-12-2.5 × 10-10 M and 7.5 × 10-13-2.5 × 10-11 M for EP and PP, respectively. The effect of various interfering agents on MOL peak current was assessed for the selectivity of the study. In the presence of 100 times more interfering agents, the RSD and recovery values were determined. The RSD values of GuaM/MOL@MIP/GCE and poly(Py-co-3-PBA)/MOL@MIP/GCE sensors were found to be 1.99% and 1.72%, respectively. Furthermore, the recovery values of the MIP-based sensors were 98.18-102.69% and 98.05-103.72%, respectively. In addition, the relative selectivity coefficient (k') of the proposed sensor was evaluated, and it exhibited good selectivity for MOL with respect to the NIP sensor. The prepared sensor was successfully applied to determine MOL in commercial serum samples and capsule form. In conclusion, the developed sensors provided excellent reproducibility, repeatability, high sensitivity, and selectivity against the MOL molecule.

Pyrene-Appended Boronic Acids on Graphene Foam Electrodes Provide Quantum Capacitance-Based Molecular Sensors for Lactate.

Molecular recognition and sensing can be coupled to interfacial capacitance changes on graphene foam surfaces linked to double layer effects and coupled to enhanced quantum capacitance. 3D graphene foam film electrodes (Gii-Sens; thickness approximately 40 µm; roughness factor approximately 100) immersed in aqueous buffer media exhibit an order of magnitude jump in electrochemical capacitance upon adsorption of a charged molecular receptor based on pyrene-appended boronic acids (here, 4-borono-1-(pyren-2-ylmethyl)pyridin-1-ium bromide, or abbreviated T1). This pyrene-appended pyridinium boronic acid receptor is employed here as a molecular receptor for lactate. In the presence of lactate and at pH 4.0 (after pH optimization), the electrochemical capacitance (determined by impedance spectroscopy) doubles again. Lactic acid binding is expressed with a Hillian binding constant (Klactate = 75 mol-1 dm3 and α = 0.8 in aqueous buffer, Klactate = 460 mol-1 dm3 and α = 0.8 in artificial sweat, and Klactate = 340 mol-1 dm3 and α = 0.65 in human serum). The result is a selective molecular probe response for lactic acid with LoD = 1.3, 1.4, and 1.8 mM in aqueous buffer media (pH 4.0), in artificial sweat (adjusted to pH 4.7), and in human serum (pH adjusted to 4.0), respectively. The role of the pyrene-appended boronic acid is discussed based on the double layer structure and quantum capacitance changes. In the future, this new type of molecular capacitance sensor could provide selective enzyme-free analysis without analyte consumption for a wider range of analytes and complex environments.

Identification and quantification of N6-methyladenosine by chemical derivatization coupled with 19F NMR spectroscopy.

N 6-Methyladenosine (6mA) is a well-known prokaryotic DNA modification that has been shown to play epigenetic roles in eukaryotic DNA. Accurate detection and quantification of 6mA are prerequisites for molecular understanding of the impact of 6mA modification on DNA. However, the existing methods have several problems, such as high false-positive rate, time-consuming and complex operating procedures. Chemical sensors for the selective detection of 6mA modification are rarely reported in the literature. Fluorinated phenylboronic acid combined with 19F NMR analysis is an effective method for determining DNA or RNA modification. In this study, we presented a simple and fast chemical method for labelling the 6th imino group of 6mA using a boric-acid-derived probe. Besides, the trifluoromethyl group of trifluoromethyl phenylboronic acid (2a) could detect 6mA modification through 19F NMR. Combined with this sensor system, 6mA modification could be detected well and quickly in 6 types of deoxynucleoside mixtures and DNA samples. Taken together, the method developed in the current study has potential for specific detection of 6mA in biological samples.

Phenylboronate-salicylate ester cross-linked self-healing hydrogel composed of modified hyaluronan at physiological pH.

Several hydrogels with boronate/diol ester cross-linking have been reported. However, multiple synthetic steps or expensive reagents are required to modify some diol moieties into polymers. Therefore, diol-modified polymers, which are easily and inexpensively prepared via a single-step process, are required for the formation of boronate esters. This study reports a novel hydrogel composed of phenylboronic acid-modified hyaluronic acid and salicylic acid-modified hyaluronic acid. This hydrogel is injectable, can self-heal at physiological pH, and can be easily and inexpensively prepared. The polymer system behaved as a sol at pH 12.0 and a weak gel at pH 9.4 and 11.2, whereas it behaved as a gel over a wide pH range of 4.0-8.2. The viscoelasticity of the system decreased in response to sugar at pH 7.3. Thus, salicylic acid can be considered a promising diol moiety for hydrogel formation via boronate ester cross-linking.

Silk fibroin hydrogel adhesive enables sealed-tight reconstruction of meniscus tears.

Despite orientationally variant tears of the meniscus, suture repair is the current clinical gold treatment. However, inaccessible tears in company with re-tears susceptibility remain unresolved. To extend meniscal repair tools from the perspective of adhesion and regeneration, we design a dual functional biologic-released bioadhesive (S-PIL10) comprised of methacrylated silk fibroin crosslinked with phenylboronic acid-ionic liquid loading with growth factor TGF-ß1, which integrates chemo-mechanical restoration with inner meniscal regeneration. Supramolecular interactions of ß-sheets and hydrogen bonds richened by phenylboronic acid-ionic liquid (PIL) result in enhanced wet adhesion, swelling resistance, and anti-fatigue capabilities, compared to neat silk fibroin gel. Besides, elimination of reactive oxygen species (ROS) by S-PIL10 further fortifies localized meniscus tear repair by affecting inflammatory microenvironment with dynamic borate ester bonds, and S-PIL10 continuously releases TGF-ß1 for cell recruitment and bridging of defect edge. In vivo rabbit models functionally evidence the seamless and dense reconstruction of torn meniscus, verifying that the concept of meniscus adhesive is feasible and providing a promising revolutionary strategy for preclinical research to repair meniscus tears.

A fluorescent probe for ultrarapid H2O2 detection during reagent-stimulated oxidative stress in cells and zebrafish.

Hydrogen peroxide(H2O2), as a reliable signaling biomolecule for oxidative stress, its accurate detection during agent-stimulated oxidative stress plays a vital role in pathological and physiological mechanism exploration for disease theranostics. It's necessary to develop an efficient method for their detection. In view of the advantages of fluorescent probes, we rationally constructed a novel fluorescent probe Compound 2 based on 4-(Bromomethyl)benzeneboronic acid pinacol ester_Herein, a small molecule fluorescent probe was fabricated using isoflore nitrile as fluorescent group, phenylboronic acid pinacol ester as the response group, to detect H2O2. The probe Compound 2 has a strong fluorescence intensity at 575 nm, indicating that the structure of the probe molecule is reasonably designed, and the Stokes shift is up to 172 nm. While the detection time is as low as 30 s and the LOD of the probe for H2O2 is as low as 3.7 µmol/L,the quantum yield is Φ = 40.31 %. It has been successfully used for imaging detection of H2O2 in HepG2 cells and zebrafish for its low toxicity. It can be found that this small molecule fluorescent probe can identify H2O2 in tumor cells significantly and efficiently, which would realize the early diagnosis of tumor.

In vitro activity of meropenem-vaborbactam plus aztreonam against metallo-ß-lactamase-producing Klebsiella pneumoniae.

We evaluated the in vitro activity of meropenem-vaborbactam plus aztreonam (MEV-ATM) against 140 metallo-ß-lactamase (MBL)-producing Klebsiella pneumoniae isolates. Among them, 25 isolates (17.9%) displayed minimum inhibitory concentrations (MIC) ≥ 8 µg/mL, while 112 (80.0%) had MIC ≤ 2 µg/mL. Genomic analysis and subsequent gene cloning experiments revealed OmpK36 134-135GD-insertion and increased carbapenemase gene (blaNDM-1 and blaOXA-48-like) copy numbers are the main factors responsible for MEV-ATM non-susceptibility. Notably, MEV-ATM is actively against aztreonam-avibactam-resistant mutants due to CMY-16 mutations.

A multilocus-dendritic boronic acid functionalized magnetic nanoparticle for capturing circulating tumor cells in the peripheral blood of mice with metastatic breast cancer.

BACKGROUND: Dynamic fluctuation of circulating tumor cells (CTCs) can serve as an indicator of tumor progression. However, the sensitive isolation of CTCs remains extremely challenging due to their rarity and heterogeneity. Against this dilemma, dendritic boronic acid-modified magnetic nanoparticles (MNPs) were prepared in this study, and polyethyleneimine (PEI) was utilized as a scaffold to significantly increase the number of boronic acid moieties. Then the novel developed material was applied to monitor the number of CTCs in mice with metastatic breast cancer to evaluate the therapeutic effects of matrine (Mat), doxorubicin (Dox), and Mat in combination with Dox. RESULTS: Compared to the low binding capacity of a single boronic acid ligand, dendritic boronic acid shows enhanced sensitivity in binding to sialic acid (SA), which is overexpressed in CTCs. The results showed that the capture efficiency of this modified material could achieve 94.7% and successfully captured CTCs in blood samples from mice with metastatic breast cancer. The CTC counts were consistent with the results of the pathologic examination, demonstrating the reliability and utility of the method. SIGNIFICANCE: The dendritic boronic acid nanomaterials prepared in this study showed high specificity, sensitivity, and accuracy for cancer cell capture. The approach is expected to provide new insights into cancer diagnosis, personalized therapy, and optimization of treatment regimens.

Viscoelastic stiffening of gelatin hydrogels for dynamic culture of pancreatic cancer spheroids.

The tumor microenvironment (TME) in pancreatic adenocarcinoma (PDAC) is a complex milieu of cellular and non-cellular components. Pancreatic cancer cells (PCC) and cancer-associated fibroblasts (CAF) are two major cell types in PDAC TME, whereas the non-cellular components are enriched with extracellular matrices (ECM) that contribute to high stiffness and fast stress-relaxation. Previous studies have suggested that higher matrix rigidity promoted aggressive phenotypes of tumors, including PDAC. However, the effects of dynamic viscoelastic matrix properties on cancer cell fate remain largely unexplored. The focus of this work was to understand the effects of such dynamic matrix properties on PDAC cell behaviors, particularly in the context of PCC/CAF co-culture. To this end, we engineered gelatin-norbornene (GelNB) based hydrogels with a built-in mechanism for simultaneously increasing matrix elastic modulus and viscoelasticity. Two GelNB-based macromers, namely GelNB-hydroxyphenylacetic acid (GelNB-HPA) and GelNB-boronic acid (GelNB-BA), were modularly mixed and crosslinked with 4-arm poly(ethylene glycol)-thiol (PEG4SH) to form elastic hydrogels. Treating the hybrid hydrogels with tyrosinase not only increased the elastic moduli of the gels (due to HPA dimerization) but also concurrently produced 1,2-diols that formed reversible boronic acid-diol bonding with the BA groups on GelNB-BA. We employed patient-derived CAF and a PCC cell line COLO-357 to demonstrate the effect of increasing matrix stiffness and viscoelasticity on CAF and PCC cell fate. Our results indicated that in the stiffened environment, PCC underwent epithelial-mesenchymal transition. In the co-culture PCC and CAF spheroid, CAF enhanced PCC spreading and stimulated collagen 1 production. Through mRNA-sequencing, we further showed that stiffened matrices, regardless of the degree of stress-relaxation, heightened the malignant phenotype of PDAC cells. STATEMENT OF SIGNIFICANCE: The pancreatic cancer microenvironment is a complex milieu composed of various cell types and extracellular matrices. It has been suggested that stiffer matrices could promote aggressive behavior in pancreatic cancer, but the effect of dynamic stiffening and matrix stress-relaxation on cancer cell fate remains largely undefined. This study aimed to explore the impact of dynamic changes in matrix viscoelasticity on pancreatic ductal adenocarcinoma (PDAC) cell behavior by developing a hydrogel system capable of simultaneously increasing stiffness and stress-relaxation on demand. This is achieved by crosslinking two gelatin-based macromers through orthogonal thiol-norbornene photochemistry and post-gelation stiffening with mushroom tyrosinase. The results revealed that higher matrix stiffness, regardless of the degree of stress relaxation, exacerbated the malignant characteristics of PDAC cells.

Effect of modification of penicillin-binding protein 3 on susceptibility to ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam, cefepime-taniborbactam, and cefiderocol of Escherichia coli strains producing broad-spectrum ß-lactamases.

The impact of penicillin-binding protein 3 (PBP3) modifications that may be identified in Escherichia coli was evaluated with respect to susceptibility to ß-lactam/ß-lactamase inhibitor combinations including ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam, cefepime-taniborbactam, and to cefiderocol. A large series of E. coli recombinant strains producing broad-spectrum ß-lactamases was evaluated. While imipenem-relebactam showed a similar activity regardless of the PBP3 background, susceptibility to other molecules tested was affected at various levels. This was particularly the case for ceftazidime-avibactam, aztreonam-avibactam, and cefepime-taniborbactam.

Activity of aztreonam-avibactam against Enterobacterales resistant to recently approved beta-lactamase inhibitor combinations collected in Europe, Latin America, and the Asia-Pacific Region (2020-2022).

BACKGROUND: Aztreonam-avibactam is under clinical development for treatment of infections caused by carbapenem-resistant Enterobacterales (CRE), especially those resistant to recently approved ß-lactamase inhibitor combinations (BLICs). OBJECTIVES: To evaluate a large collection of CRE isolates, including those non-susceptible to ceftazidime-avibactam, meropenem-vaborbactam, and/or imipenem-relebactam. METHODS: Overall, 24 580 Enterobacterales isolates were consecutively collected (1/patient) in 2020-2022 from 64 medical centres located in Western Europe (W-EU), Eastern Europe (E-EU), Latin America (LATAM), and the Asia-Pacific region (APAC). Of those, 1016 (4.1%) were CRE. Isolates were susceptibility tested by broth microdilution. CRE isolates were screened for carbapenemase genes by whole genome sequencing. RESULTS: Aztreonam-avibactam inhibited 99.6% of CREs at ≤8 mg/L. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam were active against 64.6%, 57.4%, and 50.7% of CRE isolates, respectively; most of the non-susceptible isolates carried metallo-beta-lactamases. Aztreonam-avibactam was active against ≥98.9% of isolates non-susceptible to these BLICs. The activity of these BLICs varied by region, with highest susceptibility rates observed in W-EU (76.9% for ceftazidime-avibactam, 72.5% for meropenem-vaborbactam, 63.8% for imipenem-relebactam) and the lowest susceptibility rates identified in the APAC region (39.9% for ceftazidime-avibactam, 37.8% for meropenem-vaborbactam, and 27.5% for imipenem-relebactam). The most common carbapenemase types overall were KPC (44.6% of CREs), NDM (29.9%), and OXA-48-like (16.0%). KPC predominated in LATAM (64.1% of CREs in the region) and W-EU (61.1%). MBL occurrence was highest in APAC (59.5% of CREs in the region), followed by LATAM (34.0%), E-EU (28.9%), and W-EU (23.6%). CONCLUSIONS: Aztreonam-avibactam demonstrated potent activity against CRE isolates resistant to ceftazidime-avibactam, meropenem-vaborbactam, and/or imipenem-relebactam independent of the carbapenemase produced.

The Rise of Boron-Containing Compounds: Advancements in Synthesis, Medicinal Chemistry, and Emerging Pharmacology.

Boron-containing compounds (BCC) have emerged as important pharmacophores. To date, five BCC drugs (including boronic acids and boroles) have been approved by the FDA for the treatment of cancer, infections, and atopic dermatitis, while some natural BCC are included in dietary supplements. Boron's Lewis acidity facilitates a mechanism of action via formation of reversible covalent bonds within the active site of target proteins. Boron has also been employed in the development of fluorophores, such as BODIPY for imaging, and in carboranes that are potential neutron capture therapy agents as well as novel agents in diagnostics and therapy. The utility of natural and synthetic BCC has become multifaceted, and the breadth of their applications continues to expand. This review covers the many uses and targets of boron in medicinal chemistry.

Injectable and Self-Curing Single-Component Hydrogel for Stem Cell Encapsulation and In Vivo Bone Regeneration.

An ideal hydrogel for stem cell therapy would be injectable and efficiently promote stem cell proliferation and differentiation in body. Herein, an injectable, single-component hydrogel with hyaluronic acid (HA) modified with phenylboronic acid (PBA) and spermidine (SM) is introduced. The resulting HAps (HA-PBA-SM) hydrogel is based on the reversible crosslinking between the diol and the ionized PBA, which is stabilized by the SM. It has a shear-thinning property, enabling its injection through a syringe to form a stable hydrogel inside the body. In addition, HAps hydrogel undergoes a post-injection "self-curing," which stiffens the hydrogel over time. This property allows the HAps hydrogel to meet the physical requirements for stem cell therapy in rigid tissues, such as bone, while maintaining injectability. The hydrogel enabled favorable proliferation of human mesenchymal stem cells (hMSCs) and promoted their differentiation and mineralization. After the injection of hMSCs-containing HAps into a rat femoral defect model, efficient osteogenic differentiation of hMSCs and bone regeneration is observed. The study demonstrates that simple cationic modification of PBA-based hydrogel enabled efficient gelation with shear-thinning and self-curing properties, and it would be highly useful for stem cell therapy and in vivo bone regeneration.

Simple Binding and Dissociation of a Sialoglycoprotein Using Boronic Acid-Modified Functional Interfaces on Microparticles.

An overexpression of sialic acid is an indicator of metastatic cancer, and selective detection of sialic acid shows potential for cancer diagnosis. Boronic acid is a promising candidate for this purpose because of its ability to specifically bind to sialic acid under acidic conditions. Notably, the binding strength can be easily modulated by adjusting the pH, which allows for a simple dissociation of the bound sialic acid. In this study, we developed 5-boronopicolinic acid (5-BPA)-modified magnetic particles (BMPs) to selectively capture sialic acid biomolecules. We successfully captured fetuin, a well-known sialoglycoprotein, on BMPs at >104 molecules/particle using an acetate buffer (pH 5.0). Facile dissociation then occurred when the system was changed to a pH 7.6 phosphate buffer. This capture-and-release process could be repeated at least five times. Moreover, this system could enrich fetuin by more than 20 times. In summary, BMPs are functional particles for facile purification and concentration through the selective capture of sialic acid proteins and can improve detection sensitivity compared with conventional methods. This technology shows potential for the detection of sialic acid overexpression by biological particles.

Peptide-Based Hydrogel Scaffold Facilitates Articular Cartilage Damage Repair.

Articular cartilage injury is a common disease in clinical medicine. Because of its special physiological structure and lack of blood, lymph, and nerves, its ability to regenerate once damaged is very limited. In this study, we designed and synthesized a series of self- and coassembled cartilage-inducing functional peptide molecules and constructed a coassembled functional peptide hydrogel based on phenylboronic acid-o-dihydroxy "click chemistry" cross-linking to promote aggregation and signal transduction of mesenchymal stem cells (MSCs) in the early stage and differentiation toward cartilage, thereby promoting the repair of cartilage damage. Three functional peptide molecules were produced using solid-phase peptide synthesis technology, yielding a purity higher than 95%. DOPA-FEFEFEFEGHSNGLPL (DFP) and PBA-FKFKFKFKGHAVDI (BFP) were coassembled at near-neutral pH to form hydrogels (C Gels) based on phenylboronic acid-o-dihydroxy click chemistry cross-linking and effectively loaded transforming growth factor (TGF)-ß1 with a release period of up to 2 weeks. Furthermore, chondrocytes and bone marrow mesenchymal stem cells (BMSCs) were cocultured with functional peptide hydrogels, and the results displayed that the coassembled functional peptide hydrogel group C Gels significantly promoted the proliferation of chondrocytes and MSCs. The chondrocyte markers collagen type I, collagen type II, and glycosaminoglycan (GAG) in the coassembled functional peptide hydrogel group were significantly higher than those in the control group, indicating that it can induce the differentiation of MSCs into cartilage. In vivo experiments demonstrated that the size and thickness of the new cartilage in the compound gel group were the most beneficial to cartilage regeneration. These results indicated that peptide hydrogels are a promising therapeutic option for cartilage regeneration.

Surface Modification of Polystyrene with Boronic Acid for Immunoaffinity-Based Cell Enrichment.

Obtaining an enriched and phenotypically pure cell population from heterogeneous cell mixtures is important for diagnostics and biosensing. Existing techniques such as fluorescent-activated cell sorting (FACS) and magnetic-activated cell sorting (MACS) require preincubation with antibodies (Ab) and specialized equipment. Cell immunopanning removes the need for preincubation and can be done with no specialized equipment. The majority of the available antibody-mediated analyte capture techniques require a modification to the Abs for binding. In this work, no antibody modification is used because we take advantage of the carbohydrate chain in the Fc region of Ab. We use boronic acid as a cross-linker to bind the Ab to a modified surface. The process allows for functional orientation and cleavable binding of the Ab. In this study, we created an immunoaffinity matrix on polystyrene (PS), an inexpensive and ubiquitous plastic. We observed a 37% increase in Ab binding compared with that of a passive adsorption approach. The method also displayed a more consistent antibody binding with 17 times less variation in Ab loading among replicates than did the passive adsorption approach. Surface topography analysis revealed that a dextran coating reduced nonspecific antibody binding. Elemental analysis (XPS) was used to characterize the surface at different stages and showed that APBA molecules can bind upside-down on the surface. While upside-down antibodies likely remain functional, their elution behavior might differ from those bound in the desired way. Cell capture experiments show that the new surface has 43% better selectivity and 2.4-fold higher capture efficiency compared to a control surface of passively adsorbed Abs. This specific surface chemistry modification will allow the targeted capture of cells or analytes with the option of chemical detachment for further research and characterization.