A double boronic acid affinity "sandwich" SERS biosensor based on magnetic boronic acid controllable-oriented imprinting for high-affinity biomimetic specific recognition and rapid detection of target glycoproteins.

Transferrin (TRF), recognized as a glycoprotein clinical biomarker and therapeutic target, has its concentration applicable for disease diagnosis and treatment monitoring. Consequently, this study developed boronic acid affinity magnetic surface molecularly imprinted polymers (B-MMIPs) with pH-responsitivity as the "capture probe" for TRF, which have high affinity similar to antibodies, with a dissociation constant of (3.82 ± 0.24) × 10-8 M, showing 7 times of reusability. The self-copolymerized imprinted layer synthesized with dopamine (DA) and 3-Aminophenylboronic acid (APBA) as double monomers avoided nonspecific binding sites and produced excellent adsorption properties. Taking the gold nanostar (AuNS) with a branch tip "hot spot" structure as the core, the silver-coated AuNS functionalized with the biorecognition element 4-mercaptophenylboronic acid (MPBA) was employed as a surface-enhanced Raman scattering (SERS) nanotag (AuNS@Ag-MPBA) to label TRF, thereby constructing a double boronic acid affinity "sandwich" SERS biosensor (B-MMIPs-TRF-SERS nanotag) for the highly sensitive detection of TRF. The SERS biosensor exhibited a detection limit for TRF of 0.004 ng/mL, and its application to spiked serum samples confirmed its reliability and feasibility, demonstrating significant potential for clinical TRF detection. Moreover, the SERS biosensor designed in this study offers advantages in stability, detection speed (40 min), and cost efficiency. The portable Raman instrument for SERS detection fulfills the requirements for point-of-care testing.

Colorimetric Immunoassays with Boronic Acid-Decorated, Peroxidase-like Metal-Organic Frameworks as the Carriers of Antibodies and Enzymes.

The sensitivity of immunoassays is generally limited by the low signal reporter/recognition element ratio. Nanomaterials serving as the carriers can enhance the loading number of signal reporters, thus improving the detection sensitivity. However, the general immobilization strategies, including direct physical adsorption and covalent coupling, may cause the random orientation and conformational change in proteins, partially or completely suppressing the enzymatic activity and the molecular recognition ability. In this work, we proposed a strategy to load recognition elements of antibodies and enzyme labels using boronic acid-modified metal-organic frameworks (MOFs) as the nanocarriers for signal amplification. The conjugation strategy was proposed based on the boronate ester interactions between the carbohydrate moieties in antibodies and enzymes and the boronic acid moieties on MOFs. Both enzymes and MOFs could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2, therefore achieving dual signal amplification. To indicate the feasibility and sensitivity of the strategy, colorimetric immunoassays of prostate specific antigen (PSA) were performed with boronic acid-modified Cu-MOFs as peroxidase mimics to catalyze TMB oxidation and nanocarriers to load antibody and enzyme (horseradish peroxidase, HRP). According to the change in the absorbance intensity of the oxidized TMB (oxTMB), PSA at the concentration range of 1~250 pg/mL could be readily determined. In addition, this work presented a site-specific and oriented conjugation strategy for the modification of nanolabels with recognition elements and signal reporters, which should be valuable for the design of novel biosensors with high sensitivity and selectivity.

Covalent post-synthetic modification of MOFs as a fluorescent sensor for the efficient detection of the biomarker of cystinuria.

Cystinuria is a genetic disorder, and in severe cases, it might lead to kidney failure. As an important biomarker for cystinuria, the level of arginine (Arg) in urine is a vital indicator for cystinuria screening. Therefore, it is urgently needed to detect Arg with high selectivity and sensitivity. In this work, a boric acid functionalized Zr-based metal-organic framework UiO-PhbA is prepared by grafting phenylboronic acid on UiO-66-NH2 through a Schiff base reaction using a covalent post-synthesis modification (CPSM) strategy. The prepared UiO-PhbA exhibits a sensitive and specific fluorescence "turn-on" response to Arg and can be exploited to detect Arg in human serum and urine samples with a broad linear range of 0.6-350 µM and low limit of detection (LOD) of 18.45 nM. This study provides a new and reliable rapid screening protocol for sulfite oxidase deficiency-related diseases.

Cryogel with Modular and Clickable Building Blocks: Toward the Ultimate Ideal Macroporous Medium for Bacterial Separation.

The lack of practical platforms for bacterial separation remains a hindrance to the detection of bacteria in complex samples. Herein, a composite cryogel was synthesized by using clickable building blocks and boronic acid for bacterial separation. Macroporous cryogels were synthesized by cryo-gelation polymerization using 2-hydroxyethyl methacrylate and allyl glycidyl ether. The interconnected macroporous architecture enabled high interfering substance tolerance. Nanohybrid nanoparticles were prepared via surface-initiated atom transfer radical polymerization and immobilized onto cryogel by click reaction. Alkyne-tagged boronic acid was conjugated to the composite for specific bacteria binding. The physical and chemical characteristics of the composite cryogel were analyzed systematically. Benefitting from the synergistic, multiple binding sites provided by the silica-assisted polymer, the composite cryogel exhibited excellent affinity toward S. aureus and Salmonella spp. with capacities of 91.6 × 107 CFU/g and 241.3 × 107 CFU/g in 0.01 M PBS (pH 8.0), respectively. Bacterial binding can be tuned by variations in pH and temperature and the addition of monosaccharides. The composite was employed to separate S. aureus and Salmonella spp. from spiked tap water, 40% cow milk, and sea cucumber enzymatic hydrolysate, which resulted in high bacteria separation and demonstrated remarkable potential in bacteria separation from food samples.

Stereospecific Enzymatic Conversion of Boronic Acids to Amines.

Boronic acids and esters are highly regarded for their safety, unique reactivity, and versatility in synthesizing a wide range of small molecules, bioconjugates, and materials. They are not exploited in biocatalytic synthesis, however, because enzymes that can make, break, or modify carbon-boron bonds are rare. We wish to combine the advantages of boronic acids and esters for molecular assembly with biocatalysis, which offers the potential for unsurpassed selectivity and efficiency. Here, we introduce an engineered protoglobin nitrene transferase that catalyzes the new-to-nature amination of boronic acids using hydroxylamine. Initially targeting aryl boronic acids, we show that the engineered enzyme can produce a wide array of anilines with high yields and total turnover numbers (up to 99% yield and >4000 TTN), with water and boric acid as the only byproducts. We also demonstrate that the enzyme is effective with bench-stable boronic esters, which hydrolyze in situ to their corresponding boronic acids. Exploring the enzyme's capacity for enantioselective catalysis, we found that a racemic alkyl boronic ester affords an enantioenriched alkyl amine, a transformation not achieved with chemocatalysts. The formation of an exclusively unrearranged product during the amination of a boronic ester radical clock and the reaction's stereospecificity support a two-electron process akin to a 1,2-metallate shift mechanism. The developed transformation enables new biocatalytic routes for synthesizing chiral amines.

Boronic functionalized aptamer macroarrays with dual-recognition and isothermal amplification of lipopolysaccharide detection.

A highly sensitive dual-recognition fluorescence amplification method is presented for lipopolysaccharide (LPS) detection based on boronic functionalized aptamer macroarrays with dual-recognition and isothermal amplification. The surface of the polystyrene microplate was firstly carboxylated, and then, 3-aminophenylboronic acid was conjugated to the carboxyl groups through EDC/NHS reaction, creating boronic acid groups as the capture moiety for LPS. A recognition DNA aptamer labeled with the fluorescent dye 6-FAM, which exhibits specificity towards LPS, was selected as the signal reporting moiety. By introducing primers and Klenow enzyme, the fluorescent-labeled aptamers are released from the microplate bottom, and double-stranded structures were formed via isothermal amplification. The addition of SYBR Green I, which strongly fluoresces upon binding to the double-stranded structures, enables signal amplification and detection. This detection method exhibits a linear range of 1-10,000 ng/mL and has a detection limit as low as 401.93 pg/mL. This analytical approach shows high selectivity and sensitivity and may serve as a universal platform in lipopolysaccharide detection.

Palladium-catalyzed Suzuki-Miyaura cross-couplings of stable glycal boronates for robust synthesis of C-1 glycals.

C-1 Glycals serve as pivotal intermediates in synthesizing diverse C-glycosyl compounds and natural products, necessitating the development of concise, efficient and user-friendly methods to obtain C-1 glycosides is essential. The Suzuki-Miyaura cross-coupling of glycal boronates is notable for its reliability and non-toxic nature, but glycal donor stability remains a challenge. Herein, we achieve a significant breakthrough by developing stable glycal boronates, effectively overcoming the stability issue in glycal-based Suzuki-Miyaura coupling. Leveraging the balanced reactivity and stability of our glycal boronates, we establish a robust palladium-catalyzed glycal-based Suzuki-Miyaura reaction, facilitating the formation of various C(sp2)-C(sp), C(sp2)-C(sp2), and C(sp2)-C(sp3) bonds under mild conditions. Notably, we expand upon this achievement by developing the DNA-compatible glycal-based cross-coupling reaction to synthesize various glycal-DNA conjugates. With its excellent reaction reactivity, stability, generality, and ease of handling, the method holds promise for widespread appication in the preparation of C-glycosyl compounds and natural products.

Synthesis of Boronate Affinity-Based Oriented Dummy Template-Imprinted Magnetic Nanomaterials for Rapid and Efficient Solid-Phase Extraction of Ellagic Acid from Food.

Ellagic acid (EA) is a natural polyphenol and possesses excellent in vivo bioactivity and antioxidant behaviors, which play an important role in the treatment of oxidative stress-related diseases, such as cancer. Additionally, EA is also known as a skin-whitening ingredient. The content of EA would determine its efficacy. Therefore, the accurate analysis of EA content can provide more information for the scientific consumption of EA-rich foods and cosmetics. Nevertheless, the analysis of EA in these samples is challenging due to the low concentration level and the presence of interfering components with high abundance. Molecularly imprinted polymers are highly efficient pretreatment materials in achieving specific recognition of target molecules. However, the traditional template molecule (EA) could not be absolutely removed. Hence, template leakage continues to occur during the sample preparation process, leading to a lack of accuracy in the quantification of EA in actual samples, particularly for trace analytes. In addition, another drawback of EA as an imprinting template is that EA possesses poor solubility and a high price. Gallic acid (GA), called dummy templates, was employed for the synthesis of MIPs as a solution to these challenges. The approach used in this study was boronate affinity-based oriented surface imprinting. The prepared dummy-imprinted nanoparticles exhibited several significant advantages, such as good specificity, high binding affinity ((4.89 ± 0.46) × 10-5 M), high binding capacity (6.56 ± 0.35 mg/g), fast kinetics (6 min), and low binding pH (pH 5.0) toward EA. The reproducibility of the dummy-imprinted nanoparticles was satisfactory. The dummy-imprinted nanoparticles could still be reused even after six adsorption-desorption cycles. In addition, the recoveries of the proposed method for EA at three spiked levels of analysis in strawberry and pineapple were 91.0-106.8% and 93.8-104.0%, respectively, which indicated the successful application to real samples.

Berberine encapsulated phenylboronic acid-conjugated pullulan nanoparticles: Synthesis, characterization and anticancer activity validated in A431 skin cancer cells and 3D spheroids.

Polysaccharide-based drug delivery systems are in high demand due to their biocompatibility, non-toxicity, and low-cost. In this study, sialic acid receptor targeted 4-carboxy phenylboronic acid modified pullulan-stearic acid conjugate (4-cPBA-PUL-SA) was synthesized and characterized for the delivery of Berberine (BBR). BBR-loaded 4-cPBA-PUL-SA nanoparticles (BPPNPs) were monodispersed (PDI: 0.238 ± 0.07), with an average hydrodynamic particle size of 191.6 nm and 73.6 % encapsulation efficiency. BPPNPs showed controlled BBR release and excellent colloidal stability, indicating their potential for drug delivery application. The cytotoxicity results indicated that BPPNPs exhibited dose and time-dependent cytotoxicity against human epidermoid carcinoma cells (A431) as well as 3D spheroids. Targeted BPPNPs demonstrated significantly higher anticancer activity compared to BBR and non-targeted BPNPs. The IC50 values for BPPNPs (2.29 µg/ml) were significantly lower than BPNPs (4.13 µg/ml) and BBR (19.61 µg/ml), indicating its potential for skin cancer treatment. Furthermore, CSLM images of A431 cells and 3D spheroids demonstrated that BPPNPs have higher cellular uptake and induced apoptosis compared to free BBR and BPNPs. In conclusion, BPPNPs demonstrate promising potential as an effective drug delivery system for skin cancer therapy.

Phenylboronic acid functionalized dextran loading curcumin as nano-therapeutics for promoting the bacteria-infected diabetic wound healing.

Chronic bacterial infections, excessive inflammation, and oxidative stress significantly hinder diabetic wound healing by prolonging the inflammatory phase and complicating the healing process. In this study, phenylboronic acid functionalized dextran (PODP) was developed to encapsulate curcumin, referred to as PODP@Cur. Experimental results indicate that PODP significantly improves the water solubility of curcumin and exhibits synergistic biological activity both in vitro and in vivo. PODP@Cur is capable of accelerating drug release under the pathological microenvironment with ROS accumulation. Furthermore, phenylboronic acid (PBA) has demonstrated potential for targeted bacterial drug delivery, enhancing antibacterial efficacy and trapping free LPS/PGN from dead bacteria to reduce undesirable inflammation. In a diabetic mouse model, PODP@Cur exhibits an excellent antibacterial, anti-inflammatory and antioxidant activities to ultimately promote the efficient and safe wound healing. Due to the specific interaction between PBA and LPS, PODP@Cur could enhance antibacterial activity against bacteria, reduce toxic side effects on normal cells, and alleviate the LPS-mediated pro-inflammatory pathological microenvironment. Therefore, PODP@Cur is capable of being exploited as an efficient and safe candidate for promoting the bacteria-infected diabetic wound healing.

Dynamic Covalent Boronate Chemistry Accelerates the Screening of Polymeric Gene Delivery Vectors via In Situ Complexation of Nucleic Acids.

Gene therapy provides exciting new therapeutic opportunities beyond the reach of traditional treatments. Despite the tremendous progress of viral vectors, their high cost, complex manufacturing, and side effects have encouraged the development of nonviral alternatives, including cationic polymers. However, these are less efficient in overcoming cellular barriers, resulting in lower transfection efficiencies. Although the exquisite structural tunability of polymers might be envisaged as a versatile tool for improving transfection, the need to fine-tune several structural parameters represents a bottleneck in current screening technologies. By taking advantage of the fast-forming and strong boronate ester bond, an archetypal example of dynamic covalent chemistry, a highly adaptable gene delivery platform is presented, in which the polycation synthesis and pDNA complexation occur in situ. The robustness of the strategy entitles the simultaneous evaluation of several structural parameters at will, enabling the accelerated screening and adaptive optimization of lead polymeric vectors using dynamic covalent libraries.

Borate bonds-containing pH-responsive chitosan hydrogel for postoperative tumor recurrence and wound infection prevention.

Chitosan has been widely used in biomedical fields due to its good antibacterial properties, excellent biocompatibility, and biodegradability. In this study, a pH-responsive and self-healing hydrogel was synthesized from 3-carboxyphenylboronic acid grafted with chitosan (CS-BA) and polyvinyl alcohol (PVA). The dynamic boronic ester bonds and intermolecular hydrogen bonds are responsible for the hydrogel formation. By changing the mass ratio of CS-BA and PVA, the tensile stress and compressive stress of hydrogel can controlled in the range of 0.61 kPa - 0.74 kPa and 295.28 kPa - 1108.1 kPa, respectively. After doping with tannic acid (TA)/iron nanocomplex (TAFe), the hydrogel successful killed tumor cells through the near infrared laser-induced photothermal conversion and the TAFe-triggered reactive oxygen species generation. Moreover, the photothermal conversion of the hydrogel and the antibacterial effect of CS and TA give the hydrogel a good antibacterial effect. The CS-BA/PVA/TAFe hydrogel exhibit good in vivo and in vitro anti-tumor recurrence and antibacterial ability, and therefore has the potential to be used as a powerful tool for the prevention of local tumor recurrence and bacterial infection after surgery.

Boron Neutron Capture Therapy Enhanced by Boronate Ester Polymer Micelles: Synthesis, Stability, and Tumor Inhibition Studies.

Boron neutron capture therapy (BNCT) targets invasive, radioresistant cancers but requires a selective and high B-10 loading boron drug. This manuscript investigates boron-rich poly(ethylene glycol)-block-(poly(4-vinylphenyl boronate ester)) polymer micelles synthesized via atom transfer radical polymerization for their potential application in BNCT. Transmission electron microscopy (TEM) revealed spherical micelles with a uniform size of 43 ± 10 nm, ideal for drug delivery. Additionally, probe sonication proved effective in maintaining the micelles' size and morphology postlyophilization and reconstitution. In vitro studies with B16-F10 melanoma cells demonstrated a 38-fold increase in boron accumulation compared to the borophenylalanine drug for BNCT. In vivo studies in a B16-F10 tumor-bearing mouse model confirmed enhanced tumor selectivity and accumulation, with a tumor-to-blood (T/B) ratio of 2.5, surpassing BPA's T/B ratio of 1.8. As a result, mice treated with these micelles experienced a significant delay in tumor growth, highlighting their potential for BNCT and warranting further research.

Nordihydroguaiaretic Acid-Cross-Linked Phenylboronic Acid-Functionalized Polyplex Micelles for Anti-angiogenic Gene Therapy of Orthotopic and Metastatic Tumors.

Polyplexes are required to be equipped with multiple functionalities to accomplish adequate structure stability and gene transfection efficacy for gene therapy. Herein, a 4-carboxy-3-fluorophenylboronic acid (FPBA)-functionalized block copolymer of PEG-b-PAsp(DET/FBA) and PAsp(DET/FBA) (abbreviated as PB and HB) was synthesized and applied for engineering functional polyplex micelles (PMs) through ionic complexation with pDNA followed by strategic cross-linking with nordihydroguaiaretic acid (NDGA) in respect to the potential linkage of polyphenol and FPBA moieties. In relation to polyplex micelles void of cross-linking, the engineered multifunctional polyplex micelles (PBHBN-PMs) were determined to possess improved structural tolerability against the exchange reaction with charged species. Besides, the FPBA/NDGA cross-linking appeared to be selectively cleaved in the acidic endosomal compartments but not the neutral milieu. Furthermore, the PBHB-PMs with the optimal FPBA/NDGA cross-linking degree were identified to possess appreciable cellular uptake and endosomal escape activities, eliciting a significantly high level of gene expression relative to P-PMs and PB-PMs. Eventually, in vivo antitumor therapy by our proposed multifunctional PMs appeared to be capable of facilitating expression of the antiangiogenic genomic payloads (sFlt-1 pDNA) via systemic administration. The enriched antiangiogenic sFlt-1 in the tumors could silence the activities of angiogenic cytokines for the inhibited neo-vasculature and the suppressed growth of orthotopic 4T1 tumors. Of note, the persistent expression of the antiangiogenic sFlt-1 is also presumed to migrate into the blood circulation, thereby accounting for an overall antiangiogenic environment in preventing the potential pulmonary metastasis. Hence, our elaborated multifaceted PMs inspired fascinating potential as an intriguing gene delivery system for the treatment of clinical solid tumors and metastasis.

Thiol-yne click post-synthesis of phenylboronic acid-functionalized magnetic cyclodextrin microporous organic network for selective and efficient extraction of antiepileptic drugs.

Owing to their incomplete digestion in the human body and inadequate removal by sewage treatment plants, antiepileptic drugs (AEDs) accumulate in water bodies, potentially affecting the exposed humans and aquatic organisms. Therefore, sensitive and reliable detection methods must be urgently developed for monitoring trace AEDs in environmental water samples. Herein, a novel phenylboronic acid-functionalized magnetic cyclodextrin microporous organic network (Fe3O4@CD-MON-PBA) was designed and synthesized via the thiol-yne click post-modification strategy for selective and efficient magnetic solid-phase extraction (MSPE) of trace AEDs from complex sample matrices through the specific B-N coordination, π-π, hydrogen bonding, electrostatic, and host-guest interactions. Fe3O4@CD-MON-PBA exhibited a large surface area (118.5 m2 g-1), rapid magnetic responsiveness (38.6 emu g-1, 15 s), good stability and reusability (at least 8 times), and abundant binding sites for AEDs. Under optimal extraction conditions, the proposed Fe3O4@CD-MON-PBA-MSPE-HPLC-UV method exhibited a wide linear range (0.5-1000 µg L-1), low limits of detection (0.1-0.5 µg L-1) and quantitation (0.3-2 µg L-1), good anti-interference ability, and large enrichment factors (92.2-104.3 to 92.3-98.0) for four typical AEDs. This work confirmed the feasibility of the thiol-yne click post-synthesis strategy for constructing novel and efficient multifunctional magnetic CD-MONs for sample pretreatment and elucidated the significance of B-N coordination between PBA and N-containing AEDs.

Amonafide-based H2O2-responsive theranostic prodrugs: Exploring the correlation between H2O2 level and anticancer efficacy.

Leveraging the elevated hydrogen peroxide (H2O2) levels in cancer cells, H2O2-activated prodrugs have emerged as promising candidates for anticancer therapy. Notably, the efficacy of these prodrugs is influenced by the varying H2O2 levels across different cancer cell types. In this context, we have developed a novel H2O2-activated prodrug, PBE-AMF, which incorporates a phenylboronic ester (PBE) motif. Upon H2O2 exposure, PBE-AMF liberates the fluorescent and cytotoxic molecule amonafide (AMF), functioning as a theranostic agent. Our studies with PBE-AMF have demonstrated a positive correlation between intracellular H2O2 concentration and anticancer activity. The breast cancer cell line MDA-MB-231, characterized by high H2O2 content, showed the greatest susceptibility to this prodrug. Subsequently, we replaced the PBE structure with phenylboronic acid (PBA) to obtain the prodrug PBA-AMF, which exhibited enhanced stability, aqueous solubility, and tumor cell selectivity. This selectivity is attributed to its affinity for sialic acid, which is overexpressed on the surfaces of cancer cells. In vitro assays confirmed that PBA-AMF potently and selectively inhibited the proliferation of MDA-MB-231 cells, while sparing non-cancerous MCF-10A cells. Mechanistic investigations indicated that PBA-AMF impedes tumor proliferation by inhibiting DNA synthesis, reducing ATP levels, inducing apoptosis, and arresting the cell cycle. Our work broadens the range of small molecule H2O2-activated anticancer theranostic prodrugs, which are currently limited in number. We anticipate that the applications of PBA-AMF will extend to a wider spectrum of tumors and other diseases associated with increased H2O2 levels, thereby offering new horizons in cancer diagnostics and treatment.

Production of Peroxymonocarbonate by Steady-State Micromolar H2O2 and Activated Macrophages in the Presence of CO2/HCO3- Evidenced by Boronate Probes.

Peroxymonocarbonate (HCO4-/HOOCO2-) is produced by the reversible reaction of CO2/HCO3- with H2O2 (K = 0.33 M-1, pH 7.0). Although produced in low yields at physiological pHs and H2O2 and CO2/HCO3- concentrations, HCO4- oxidizes most nucleophiles with rate constants 10 to 100 times higher than those of H2O2. Boronate probes are known examples because HCO4- reacts with coumarin-7-boronic acid pinacolate ester (CBE) with a rate constant that is approximately 100 times higher than that of H2O2 and the same holds for fluorescein-boronate (Fl-B) as reported here. Therefore, we tested whether boronate probes could provide evidence for HCO4- formation under biologically relevant conditions. Glucose/glucose oxidase/catalase were adjusted to produce low steady-state H2O2 concentrations (2-18 µM) in Pi buffer at pH 7.4 and 37 °C. Then, CBE (100 µM) was added and fluorescence increase was monitored with time. The results showed that each steady-state H2O2 concentration reacted more rapidly (∼30%) in the presence of CO2/HCO3- (25 mM) than in its absence, and the data permitted the calculation of consistent rate constants. Also, RAW 264.7 macrophages were activated with phorbol 12-myristate 13-acetate (PMA) (1 µg/mL) at pH 7.4 and 37 °C to produce a time-dependent H2O2 concentration (8.0 ± 2.5 µM after 60 min). The media contained 0, 21.6, or 42.2 mM HCO3- equilibrated with 0, 5, or 10% CO2, respectively. In the presence of CBE or Fl-B (30 µM), a time-dependent increase in the fluorescence of the bulk solution was observed, which was higher in the presence of CO2/HCO3- in a concentration-dependent manner. The Fl-B samples were also examined by fluorescence microscopy. Our results demonstrated that mammalian cells produce HCO4- and boronate probes can evidence and distinguish it from H2O2 under biologically relevant concentrations of H2O2 and CO2/HCO3-.

Study on the creation of boronate affinity-based oriented imprinted silica nanoparticles and their selective recognition toward glycopeptide antibiotics in food and water.

Taking into account the drug resistance of antibiotics, teicoplanin has been banned in the veterinary field. Also, it brings threat to people's health when they eat foods containing teicoplanin residue. In addition, the abuse of teicoplanin in humans and food animals also poses a potential risk to water. Therefore, it is crucial to purify teicoplanin from food before quantifying its amount. In this study, researchers employed boronate affinity-based controlled oriented surface imprinting technique to produce molecularly imprinted polymers (MIPs) for the isolation of teicoplanin. The 3-fluoro-4-formylphenylboronic acid-functionalized silica nanoparticle substrate was first used as the supporting material for immobilizing teicoplanin. Next, the substrate surface was coated with an imprinting coating whose thickness could be controlled, produced through the self-copolymerization of dopamine and m-aminophenylboronic acid (APBA) in water. After the template was removed, 3D cavities that matched the template were created in the imprinting layer. The prepared teicoplanin-imprinted silica nanoparticles exhibited several significant satisfactory results such as good specificity, high binding capacity (46.9 ± 2.3 mg g-1), moderate binding constant ((5.46 ± 0.18) × 10-5 M-1), fast kinetics (8 min) and low binding pH (pH 5.0) toward teicoplanin. The teicoplanin-imprinted silica nanoparticles could still be reused after seven cycles of adsorption-desorption, which indicated a high chemical stability. In addition, recoveries of the proposed method for teicoplanin at three spiked levels in milk and water ranged from 91.8 to 105.6% and 92.3 to 97.4%, respectively. The teicoplanin-imprinted silica nanoparticles are capable of identifying the target teicoplanin in real samples in a simple, fast, selective and efficient manner.

Optimization of α-amido boronic acids via cryo-electron microscopy analysis: Discovery of a novel highly selective immunoproteasome subunit LMP7 (ß5i)/LMP2 (ß1i) dual inhibitor.

The immunoproteasome subunit LMP7 (ß5i)/LMP2 (ß1i) dual blockade has been reported to suppress B cell differentiation and activation, suggesting that the dual inhibition of LMP7/LMP2 is a promising approach for treating autoimmune diseases. In contrast, the inhibition of the constitutive proteasome subunit ß5c correlates with cytotoxicity against non-immune cells. Therefore, LMP7/LMP2 dual inhibitors with high selectivity over ß5c may be desirable for treating autoimmune diseases. In this study, we present the optimization and discovery of α-amido boronic acids using cryo-electron microscopy (cryo-EM). The exploitation of structural differences between the proteasome subunits led to the identification of a highly selective LMP7/LMP2 dual inhibitor 19. Molecular dynamics simulation based on cryo-EM structures of the proteasome subunits complexed with 19 explained the inhibitory activity profile. In mice immunized with 4-hydroxy-3-nitrophenylacetyl conjugated to ovalbumin, results indicate that 19 is orally bioavailable and shows promise as potential treatment for autoimmune diseases.

Optimization of boronic ester-based amphiphilic copolymers for ROS-responsive drug delivery.

This study introduces boronic ester-based ROS-responsive amphiphilic copolymers for antioxidant drug delivery. Tuning the hydrophobic/hydrophilic balance optimized the size, curcumin encapsulation, ROS-triggered release, cellular uptake, and intracellular ROS scavenging. The lead P1b formulation self-assembled into stable 10 nm micelles enabling rapid ROS-triggered curcumin release and preferential cellular internalization. P1b eliminated over 90% of pathogenic intracellular ROS within 10 minutes, demonstrating a rapid antioxidant therapy.