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Diabetes is a common chronic metabolic disease. Different types of drugs play important roles in controlling diabetes and its complications, but there are some limitations. The glucose-responsive drug delivery system is a novel technology with potential in diabetes treatment. It could automatically release drugs in response to changes in glucose levels in the body to maintain blood glucose within a normal range. The emergence of a glucose-sensitive drug delivery system provides a more intelligent and precise way to treat diabetes. The review is carried out according to the Preferred Reporting Items for Systematic Reviews (PRISMA 2020) guidelines This review focuses on the recent advances in the drugs and different systems of glucose-sensitive drug delivery, including glucose oxidase, phenylboronic acid, Concanavalin A, and other glucose-reactive systems. Furthermore, the glucose-responsive drug delivery system combined with the application applied in hydrogels, microneedles, and nanoparticles is also explored and summarized. The new platforms to sustain the release of anti-diabetic drugs could be desirable for patients. It could lead to increased adherence and glycemic outcomes for the detection and treatment of diabetes. Furthermore, given the limitations of glucose-responsive drug delivery systems, solutions and perspectives are proposed to help the understanding and application of these systems. This review will be helpful for drug discovery and treatment of diabetes from a new perspective. [ABSTRACT FROM AUTHOR]

Diabetes is a major health concern that the next-generation of on-demand insulin releasing implants may overcome via personalized therapy. Therein, 3D-printed phenylboronic acid-containing implants with on-demand glucose-triggered drug release abilities are produced using high resolution stereolithography technology. To that end, the methacrylation of phenylboronic acid is targeted following a two-step reaction. The resulting photocurable phenylboronic acid derivative is accordingly incorporated within bioinert polyhydroxyethyl methacrylate-based hydrogels at varying loadings. The end result is a sub-centimeter scaled 3D-printed bioinert implant that can be remotely activated with 1,2-diols and 1,3-diols such as glucose for on-demand drug administration such as insulin. As a proof of concept, varying glucose concentration from hypoglycemic to hyperglycemic levels readily allow the release of pinacol, i.e., a 1,2-diol-containing model molecule, at respectively low and high rates. In addition, the results demonstrated that adjusting the geometry and size of the 3D-printed part is a simple and suitable method for tailoring the release behavior and dosage. [ABSTRACT FROM AUTHOR]

Dry eye disease (DED) is a kind of multifactorial ocular surface disease that displays ocular discomfort, visual disturbance, and tear film instability. Oxidative stress is a fundamental pathogenesis in DED. An imbalance between the reactive oxygen species (ROS) level and protective enzyme action will lead to oxidative stress, cell dysfunction, tear hyperosmolarity, and inflammation. Herein, a multifunctional cerium oxide nanozyme with high ocular surface retention property was designed to neutralize over-accumulated ROS and restore redox balance. Cerium oxide nanozymes were fabricated via branched polyethylenimine-graft-poly (ethylene glycol) nucleation and dispersion, followed by phenylboronic acid (PBA) functionalization (defined as Ce@PB). Due to the dynamic chemical bonding formation between the PBA segment and the cis-diol groups in the mucin layer of the tear film, Ce@PB nanozymes possess good adhesive capability to the ocular surface, thus extending the drug's retention time. On the other hand, Ce@PB nanozymes could mimic the cascade processes of superoxide dismutase and catalase to maintain intracellular redox balance. In vitro and in vivo studies suggest that such multifunctional nanozymes possess good biocompatibility and hemocompatibility. More importantly, Ce@PB nanozymes treatment in the animal model could repair corneal epithelial defect, increase the number of goblet cells and promote tear secretion, thus achieving an effective treatment for DED. • PBA-functionalized bPEI-g-PEG-based cerium oxide (Ce@PB) nanozymes were designed and fabricated. • The Ce@PB nanozymes have superoxide dismutase (SOD) and catalase (CAT) enzyme-like activity scavenging excessive intracellular reactive oxygen species (ROS). • The Ce@PB nanozymes demonstrate extended retention on the ocular surface and can effectively treat dry eye disease. [Display omitted] [ABSTRACT FROM AUTHOR]

Introduction. In the pharmaceutical technology field there is great interest in polymers with mucoadhesive properties, as they increase the drug retention time on the mucosal surface and increase the bioavailability of the drug. There are various mucoadhesive drug delivery systems: tablets, films, gels, suspensions of micro- and nanoparticles, etc. The ability to adhesion depends on the excipients, especially on their chemical structure. Molecular weight, surface charge, flexibility of the polymer chain and the presence of various functional groups play an important role. Polymers under the trade name Eudragit®, produced by the German concern Evonik Nutrition & Care GmbH, have been used in the pharmaceutical field for several decades to produce controlled-release oral dosage forms. Eudragit® EPO (EPO) is a ternary copolymer based on methacrylic acid derivatives and has mucoadhesive properties due to the presence of dimethylamino groups in its structure. The proposed chemical modification of Eudragit® EPO with a phenylboronic acid derivative, due to the presence of hydroxyl groups in their structure, leads to additional interaction with mucin oligosaccharides, providing enhanced mucoadhesive properties of this polymer.Aim. Synthesis and study of a chemically modified Eudragit® EPO using 4-bromophenylboronic acid in order to increase the mucoadhesive properties of the copolymer for use in transmucosal drug delivery systems.Materials and methods. The synthesis of chemically modified Eudragit® EPO (BEPO) was carried out for 24 hours at 50 °C, followed by purification by dialysis using a dialysis membrane (MMO = 12–14 kDa; Medicell International Ltd, UK) for 7 days and freeze drying at –50 °C and 0.05 mbar using Heto Power Dry LL 3000 (Thermo Electron Corporation, USA) for 5 days. Confirmation of the formation of ВЕРО was carried out by ATR-FTIR spectroscopy on a Nicolet iS5 spectrometer (Thеrmо Fisher Sciеntific, USA) and 1H-NMR spectroscopy on a DPX 400 MHz device (Bruker, Germany). Thermogravimetric analysis (TGA) and modulated differential scanning calorimetry (mDSC) were performed using Discovery TGA™ and Discovery DSC™ (TA Instruments, USA), respectively. The study of mucoadhesive properties was performed by the ability to retain the copolymer on the isolated sheep nasal mucosa at 37.0 ± 0.5 °C for 30 minutes.Results and discussion. BEPO was prepared with a substitution degree of dimethylamino groups with phenylboronic acid of 25 % (BEPO25) and 50 % (BEPO50). The yields of BEPO25 and BEPO50 were 40.70 and 30.79 %. The new characteristic band appears at 1605 cm–1 in the IR spectrum of BEPO, which indicates the attachment of phenylboronic acid to EPO. In the 1H-NMR spectrum of BEPO, the formation of additional peaks in the range of 7.8 and 7.5 ppm is observed, which are absent in the EPO spectrum, which indicates the presence of phenylboronic acid. According to TGA results the samples of boronated EPO have the thermal stability similar to the original EPO. The results of DSC analysis show that the glass transition temperature (Tg) of BEPO samples is somehow higher than the original EPO, which is probably associated with a decrease in the amount of free dimethylamino groups in the terpolymer structure. BEPO50 is retained on the surface of isolated sheep nasal mucosa for 30 minutes, while EPO is washed off with artificial nasal fluid in 5 minutes.Conclusion. The development and study of BEPO is a promising direction for further use in transmucosal drug delivery systems.

This article presents a comprehensive organic chemistry experiment in which salicylaldehyde, phenylboronic acid, and aromatic amines are employed as the substrates. The selective synthesis of diarylmethyl aniline and triarylmethane could be achieved through the control of substituents. The structure of the product is characterized by ¹H NMR and 13C NMR. This experiment combines theoretical knowledge to inspire students to think about mechanisms, helps them broaden their knowledge horizons, and establishes the concept of "green chemistry" and environmental awareness. [ABSTRACT FROM AUTHOR]

Glucose-sensitive membrane has potential application in self-regulating insulin release. Phenylboronic acid (PBA) is a well-known glucose reporter. Unfortunately, most PBA-based glucose-sensitive materials are expansion-type, which are not suitable as chemical valves in membrane pores for self-regulating insulin release. According to a new glucose-sensitive mechanism, we synthesized PBA-based contraction-type glucose-sensitive liner polymer and microgels. Herein, a glucose-sensitive membrane was prepared by grafting PBA-based contraction-type glucose-sensitive linear polymer on the membrane surface. Through adjusting the chain length and chain density, the glucose-sensitivity of the membrane was optimized. The membrane can reversibly regulate insulin release at physiologically relevant glucose concentrations in simulates body fluids and fetal bovine serum. The membrane also has good stability, anti-fouling and biocompatibility. It has potential application in self-regulating insulin release. [ABSTRACT FROM AUTHOR]

In the present study, a resin is synthesized from resorcinol and formaldehyde in the presence of phenylboronic acid. Properties of resins such as free formaldehyde content, total solid content, density, gelation time, viscosity are determined. The chemical structure of the resorcinol‐formaldehyde resin and the resorcinol‐formaldehyde resin containing phenylboronic acid is confirmed by Fourier transform infrared spectroscopy (FTIR), nuclear magnetic resonance spectroscopy, X‐ray photoelectron spectroscopy (XPS), X‐ray diffraction (XRD), and scanning electron microscopy (SEM). The thermal stability and curing behaviors of the polymers are investigated by thermogravimetric analysis (TGA) and differential scanning calorimetry, respectively. Modification of the resorcinol‐formaldehyde resin with a boron source, phenylboronic acid results in a certain increase in thermal stability with a higher residual weight. The 6% PBA loaded polymer has the highest thermal efficiency, so the thermal behavior of it is investigated by curing at different temperatures. The 80 °C/4 h curing method is the most reasonable for energy savings. In differential scanning calorimetry (DSC) analysis, a 6 wt% PBA loading ratio was determined as the optimum value according to the energy requirements. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to present an innovative method for synthesizing pH-thermo-glucose responsive poly(NIPA-co-DMAEMA)-PBA hydrogel nanoparticles via single-step aqueous free radical polymerization. Methods: The synthesis process involved free radical polymerization in an aqueous solution, and the resulting nanoparticles were characterized for their physical and chemical properties by 1H NMR, Dynamic Light Scattering (DLS) and Scanning Electron Microscopy (SEM). Insulin-loaded poly(NIPA-co-DMAEMA)-PBA hydrogel nanoparticles were prepared and evaluated for their insulin capture and release properties at different pH and temperature, in addition to different glucose concentrations, with the release profile of insulin quantitatively evaluated using the Bradford method. Results: 1H NMR results confirmed successful PBA incorporation, and DLS outcomes consistently indicated a transition to a more hydrophobic state above the Lower Critical Solution Temperature (LCST) of NIPA and DMAEMA. While pH responsiveness exhibited variation, insulin release generally increased with rising pH from acidic to neutral conditions, aligning with the anticipated augmentation of anionic PBA moieties and increased hydrogel hydrophilicity. Increased insulin release in the presence of glucose, particularly for formulations with the lowest mol % PBA, along with a slight increase for the highest mol % PBA formulation when increasing glucose from 1 to 4 mg/mL, supported the potential of this approach for nanoparticle synthesis tailored for glucose-responsive insulin release. Conclusions: This work successfully demonstrates a novel method for synthesizing responsive hydrogel nanoparticles and underscores their potential for controlled insulin release in response to glucose concentrations. The observed pH-dependent insulin release patterns and the influence of PBA content on responsiveness highlight the versatility and promise of this nanoparticle synthesis approach for applications in glucose-responsive drug delivery systems. Poly(NIPA) nanoparticles containing PBA moieties are normally synthesized in two or more steps in the presence of organic solvents. Here we propose a new method for the synthesis of multiresponsive hydrogel poly(NIPA-co-DMAEMA)-PBA nanoparticles in aqueous medium in a single reaction to provide a fast and effective strategy for the production of glucose-responsive multi-systems in aqueous media from free radical polymerization [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

External stimuli-responsive worm-like micelles (WLMs) have the potential for a wide range of applications. In particular, sugar (a polyol compound)-responsive WLMs have the potential for use in smart-drug release systems. Phenylboronic acid (PBA) functions as a cis-diol sensor in a similar manner it does as a glucose sensor. Thus, WLMs, primarily composed of surfactants and PBA, are expected to function as cis-diol-responsive viscoelastic systems. PBA also reacts irreversibly with hydrogen peroxide (H2O2) and is converted into phenol and boric acid. H2O2 is one of reactive oxygen species crucial for several physiological processes. Therefore, H2O2-responsive WLMs have the potential for various applications. In this review, we describe cis-diol- and H2O2-responsive micellar systems composed of cetyltrimethylammonium bromide and PBA moieties that shift their viscosities in response to stimuli. [ABSTRACT FROM AUTHOR]

Diabetes is a common chronic metabolic disease. Different types of drugs play important roles in controlling diabetes and its complications, but there are some limitations. The glucose-responsive drug delivery system is a novel technology with potential in diabetes treatment. It could automatically release drugs in response to changes in glucose levels in the body to maintain blood glucose within a normal range. The emergence of a glucose-sensitive drug delivery system provides a more intelligent and precise way to treat diabetes. The review is carried out according to the Preferred Reporting Items for Systematic Reviews (PRISMA 2020) guidelines This review focuses on the recent advances in the drugs and different systems of glucose-sensitive drug delivery, including glucose oxidase, phenylboronic acid, Concanavalin A, and other glucose-reactive systems. Furthermore, the glucose-responsive drug delivery system combined with the application applied in hydrogels, microneedles, and nanoparticles is also explored and summarized. The new platforms to sustain the release of anti-diabetic drugs could be desirable for patients. It could lead to increased adherence and glycemic outcomes for the detection and treatment of diabetes. Furthermore, given the limitations of glucose-responsive drug delivery systems, solutions and perspectives are proposed to help the understanding and application of these systems. This review will be helpful for drug discovery and treatment of diabetes from a new perspective.

Diabetes is a major health concern that the next-generation of on-demand insulin releasing implants may overcome via personalized therapy. Therein, 3D-printed phenylboronic acid-containing implants with on-demand glucose-triggered drug release abilities are produced using high resolution stereolithography technology. To that end, the methacrylation of phenylboronic acid is targeted following a two-step reaction. The resulting photocurable phenylboronic acid derivative is accordingly incorporated within bioinert polyhydroxyethyl methacrylate-based hydrogels at varying loadings. The end result is a sub-centimeter scaled 3D-printed bioinert implant that can be remotely activated with 1,2-diols and 1,3-diols such as glucose for on-demand drug administration such as insulin. As a proof of concept, varying glucose concentration from hypoglycemic to hyperglycemic levels readily allow the release of pinacol, i.e., a 1,2-diol-containing model molecule, at respectively low and high rates. In addition, the results demonstrated that adjusting the geometry and size of the 3D-printed part is a simple and suitable method for tailoring the release behavior and dosage.

Diabetes, characterized by chronic hyperglycemia, has become a major threat to human health. A noninvasive, continuous, and rapid visual detection of glucose is still a challenge in application. In this study, one-dimensional photonic crystals (1DPCs) prepared via layer-by-layer assembling of glucose-responsive poly-(acrylamide-N,N'-methylenebis-(acrylamide)-3-acrylamide phenylboronic acid) (P-(AM-MBA-AAPBA)) nanogels and TiO2 nanoparticles are first confirmed for rapid and continuous colorimetric detection of glucose in physiological conditions. A two-step swelling mechanism of PCs was designed to speed up glucose diffusion and recognition. In detection, the PC sensor with a thickness of about 200 nm can rapidly imbue the polymer layer with water, causing the polymer layer to swiftly swell and create a pathway for mass transfer. Then, glucose molecules permeate in PC's channels and bind to phenylboronic acid (PBA) sites, prompting secondary expansion. Due to the inherent hydrophilicity of the polymer and the nanoporous structure of the TiO2 layer, PC sensors exhibit exceptional responsiveness, reaching sensing equilibrium in glucose solution within 40 s and quickly reverting to their initial state within 1 s after adding diluted hydrochloric acid. The PC sensor effectively generates optical signals across a broad glucose concentration range of 0–100 mM and realizes continuous glucose detection. Notably, they can indicate the risk of diabetes with artificial urine, which provides a strategy for noninvasive glucose detection. In addition, the adsorption and desorption processes of glucose on PC are monitored with a quartz crystal microbalance with dissipation, and the reversible swelling of the nanogel layer is revealed, which provides valuable references for the mechanism study of PC glucose sensors. [ABSTRACT FROM AUTHOR]

In our study, we designed and developed a glucose biosensor that operates without a battery or chip. This biosensor utilizes the principles of radio frequency (RF) to operate. For the construction of a glucose-sensitive interdigitated capacitor (IDC), a famous glucose-sensitive substance called phenylboronic acid (PBA) is combined with a polyvinyl chloride (PVC) and n,n-dimethylacetamide (DMAC) solution. According to the theory of radio frequency sensing, the resonance frequency shifts whenever there is a change in the capacitance of the glucose-sensitive IDC. This change is caused by the fluctuations in glucose concentrations. As far as we are aware, this is the first glucose sensor that employs the RF principle to detect changes in glucose solution concentrations using PBA as the principal glucose-sensitive material. The sensor can detect glucose levels with remarkable sensitivity, around 40.89 kHz/decade, and a broad dynamic range covering 10 μM to 1 M. Additionally, the designed biosensor has excellent linearity performance, with a value of around 0.988. The proposed glucose biosensor has several benefits: lightweight, inexpensive, easy to build, and an acceptable selectivity response. Our study concludes by comparing the proposed RF sensor's effectiveness to that of existing glucose sensors, which it outperforms. [ABSTRACT FROM AUTHOR]

The prevalence of drug‐resistant bacterial pathogens foreshadows a healthcare crisis. Calcium‐dependent antibiotics (CDAs) are promising candidates to combat infectious diseases as many of them show modes of action (MOA) orthogonal to widespread resistance mechanisms. The calcium dependence is nonetheless one of the hurdles toward realizing their full potential. Using laspartomycin C (LspC) as a model, we explored the possibility of reducing, or even eliminating, its calcium dependence. We report herein a synthetic LspC analogue (B1) whose activity no longer depends on calcium and is instead induced by phenylboronic acid (PBA). In LspC, Asp1 and Asp7 coordinate to calcium to anchor it in the active conformation; these residues are replaced by serine in B1 and condense with PBA to form a boronic ester with the same anchoring effect. Using thin‐layer chromatography, MS, NMR, and complementation assays, we demonstrate that B1 inhibits bacterial growth via the same MOA as LspC, i.e. sequestering the cell wall biosynthetic intermediate undecaprenyl phosphate. B1 is as potent and effective as LspC against several Gram‐positive bacteria, including methicillin‐resistant Staphylococcus aureus and vancomycin‐resistant Enterococcus. Our success in converting a CDA to a boron‐dependent antibiotic opens a new avenue in the design and functional control of drug molecules. [ABSTRACT FROM AUTHOR]

Abstract 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.

A novel phenylboronic acid and amino bifunctional modified silica gel (SiO2-NH2-FPBA) was prepared, which was 30–80 μm, had a pore size of 8.69 nm, a specific surface area of 206.89 m2/g, was stable at low temperature, and contained 0.4793 mmol/g of the phenylboronic acid group and 1.6377 mmol/g of the amino group. It was used to develop a rapid separation method for phenolic acids. The results showed that it could adsorb 93.64 mg/g caffeic acid, 89.35 mg/g protocatechuic acid and 79.66 mg/g gallic acid. The adsorption process was consistent with the pseudo-second-order model (R2 > 0.99), and fitted the Langmuir isotherm model well (R2 > 0.99). CH3COOH could effectively desorb phenolic acids (>90%) and did not destroy their structures. When SiO2-NH2-FPBA was added to crude extract of Clerodendranthus spicatus, 93.24% of the phenolic acids could be captured, and twenty-two kinds of phenolic acids were identified by Q Exactive HF LC-MS. Furthermore, the isolated phenolic acids from Clerodendranthus spicatus possessed great DPPH, ABTS, and hydroxyl radicals scavenging activities and ferric reducing power. They also demonstrated effective inhibition of α-amylase and α-glucosidase activities (IC50 = 110.63 ± 3.67 μg/mL and 64.76 ± 0.30 μg/mL, respectively). The findings indicate that SiO2-NH2-FPBA has significant potential in practical applications of separating active constituents from natural resources. [ABSTRACT FROM AUTHOR]

Nanopore sensing measures the changes in charge and physical state around the nanopores as changes in ionic current. In this study, we performed vancomycin (VCM) sensing with nanopores modified via Au−S bonds with dithiobis(4‐butyrylamino‐m‐phenylboronic acid) (DTBA‐PBA), a derivative of phenylboronic acid (PBA) bearing a thiol. First, we modified a 3‐mm‐diameter Au electrode with a DTBA‐PBA self‐assembled monolayer (SAM) to confirm the VCM response of the PBA interface by cyclic voltammetry. DTBA‐PBA was then immobilized in the same manner on a nanopore pipette coated with an Au layer. We measured the VCM concentration from the change in ion current using the nanopore pipette. A VCM concentration‐dependent ionic current response was observed in the range of 0.01–1 mM. Many kinds of pharmaceuticals can bind to PBA; therefore, this method could be used for quick, easy, in situ quantification of not only VCM but also other pharmaceuticals with serious side effects. [ABSTRACT FROM AUTHOR]

Herein, binding affinities of one‐walled meso‐phenylboronic acid functionalized calix[4]pyrroles (C4Ps, 3 a & 3 b) with diverse anions including spherical, linear, trigonal, and tetrahedral through UV‐Vis spectroscopy have successfully been revealed in acetonitrile solvent. The C4P derivative 3 b was newly synthesized from an easily accessible 3‐acetylphenylboronic acid via both conventional as well as green protocols. Structure of the final compound 3 b and the dipyrromethane (DPM) 2 b, were unambiguously established by means of 1H‐NMR, 13C‐NMR, and HRMS spectral data. From the outcomes of the UV‐Vis titrations of 3 a/3 b with different anions (e. g., F−, Cl−, Br−, I−, NO3−, HSO4−, H2PO4−, CH3COO−, & SCN−), used as their tetrabutylammonium (TBA) salts in CH3CN, 1 : 1 stoichiometric binding mode were observed from the BindFit v0.5 and Job plots. Overall, the binding affinity of receptor (3 b) with different anions were found higher in comparison to the receptor (3 a), presumably due to more cooperative NH and/or OH hydrogen bonding interactions. On the basis of varied size of halide ions, typical trend of anion binding affinity i. e., F−>Cl−>Br−>I−, was detected with increase in size of halide ions from F− to I−. Hopefully, these anion binding investigations with C4P‐based meso‐functionalized architectures will open new possibilities to the researchers to generate even more interesting artificial anion receptors based on vital boronic acid functionality, as biological and chemical importance of the anions is continuously motivating the synthetic chemists worldwide. [ABSTRACT FROM AUTHOR]

Hydrogelators generate hydrogels when dissolved in water, forming a network of interlocking chains on the nanoscale level. For their unique viscoelastic, mechanical, and swelling properties, these hydrogels have found various applications, such as water absorbent, biocompatible, and biodegradable scaffolds in tissue engineering and nanocarriers in drug delivery. When measuring the solubility of p-, m-, and o-isobutoxy derivatives of phenylboronic acid, we identified m-isobutoxyphenylboronic acid (PBA) as a low-molecular-weight hydrogelator, the first of which solely based on phenylboronic acid. At low concentrations, PBA gelated water into a network of cross-linked nanofibers combining amorphous and crystalline phases, as shown by electron and optical microscopy, rheometry, and differential scanning calorimetry and confirmed by small- and wide-angle X-ray scattering. By increasing the PBA concentration, we were able to tailor the elastic modulus (G′) of PBA hydrogels across 2 orders of magnitude, from 2.5 to 103 kPa. In turn, at a specific PBA concentration, we tuned their viscoelastic properties by adding urea, thereby adjusting the gelation temperature between 62 and 56 °C and G′ at body temperature between 63.4 and 30.4 kPa. Moreover, PBA hydrogels dissolved in response to various triggers (pH increase, H2O2 and cyclodextrin addition) and selectively absorbed dyes for liquid mixture separation. These findings demonstrate that PBA has a high potential as a biodegradable, multistimuli-responsive, low-molecular-weight hydrogelator for bioapplications. [ABSTRACT FROM AUTHOR]

A template method for synthesis of B-doped graphene-like carbon nanomaterial (B-graphene-like carbon) with high surface area has been developed. In this method, magnesium oxide is used as a template where a carbon layer doped with boron atoms is deposited. Magnesium oxide carbonization was performed in an autoclave at 600 °C and 5 atm pressure using phenylboronic acid (FBA) dissolved in an ethanol-acetone mixture. Then, magnesium oxide from the С—B/MgO composite was dissolved in hydrochloric acid. The obtained B- graphene-like carbon was studied by IR spectroscopy, electron microscopy, XPS methods and quantum chemical calculations. B-graphene-like carbon contains 3–6 carbon layers and 0.2 wt% B. Structure of carbon net with embedded boron fragment has been proposed as the result of performed studies. [ABSTRACT FROM AUTHOR]

Interleukin 2 (IL-2) is widely used as an active immunotherapeutic agent in clinical metastatic cancers. However, its therapeutic concentrations do not last long due to its short half-life. Thus, only a transient proliferation of the anti-cancer CD8+ T cells can be achieved, resulting in poor efficacy. Therefore, the aim of this work was to create a system that promotes CD8+ T cell proliferation at the tumor site using IL-2 persistently present and activates an anti-cancer immune response. This goal was achieved by the design of the IL-2-loaded polypeptide nanoparticles (P-IL-2) where methoxy poly(ethylene glycol) block poly-[(N-2-hydroxyethyl)-aspartamide] phenylboronic acid was used to encapsulate IL-2 through boron-nitrogen coordination with poly(L-lysine). P-IL-2 significantly prolonged the circulation time of IL-2 and achieved a selective drug release at the tumor site in the presence of high levels of reactive oxygen species, thus activating an anti-cancer immune response and exerting a better anti-cancer effect. The half-life of P-IL-2 was 3.15-fold higher than that of IL-2, and the quantity of CD8+ T cells after using P-IL-2 was 1.89-fold higher than that after using IL-2. In addition, the combination of P-IL-2 and anti-CTLA-4 monoclonal antibody resulted in an enhanced immune activation. Hence, this work provides a new approach to improve the efficacy of IL-2 in anti-cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Chemotherapy is currently one of the most widely used treatments for cancer. However, traditional chemotherapy drugs normally have poor tumor selectivity, leading to insufficient accumulation at the tumor site and high systemic cytotoxicity. To address this issue, we designed and prepared a boronic acid/ester-based pH-responsive nano-drug delivery system that targets the acidic microenvironment of tumors. We synthesized hydrophobic polyesters with multiple pendent phenylboronic acid groups (PBA-PAL) and hydrophilic PEGs terminated with dopamine (mPEG-DA). These two types of polymers formed amphiphilic structures through phenylboronic ester linkages, which self-assembled to form stable PTX-loaded nanoparticles (PTX/PBA NPs) using the nanoprecipitation method. The resulting PTX/PBA NPs demonstrated excellent drug encapsulation efficiency and pH-triggered drug-release capacity. In vitro and in vivo evaluations of the anticancer activity of PTX/PBA NPs showed that they improved the pharmacokinetics of drugs and exhibited high anticancer activity while with low systemic toxicity. This novel phenylboronic acid/ester-based pH-responsive nano-drug delivery system can enhance the therapeutic effect of anticancer drugs and may have high potential for clinical transformations. [ABSTRACT FROM AUTHOR]

A polyethylene glycol （PEG） derivative PBA-PEG-SA, which connects phenylboronic acid （PBA） with an amide bond at one end and stearic acid （SA） with an ester bond at the other end, is synthesized by substitution reaction and esterification reaction. And a liposome with pH response characteristics is prepared by co-assembly of PBA-PEG-SA with distearyl choline phosphate （DSCP） and cholesterol （CH）. When PBA-PEG-SA, cholesterol and DSCP are assembled at a mass ratio of 1∶3∶10, the particle size of the prepared liposome is 115 nm, and it could maintain good particle size stability within 20 d. In addition, the liposome has good biocompatibility. When the concentration reaches 800 µg/mL, the survival rate of mouse embryonic fibroblast （NIH-3T3）and hepatoma cell （HepG2） can reach more than 90%. At the same time, after loading doxorubicin （Dox), compared with DSCP liposomes （Lip/Dox）, Fru/PBA/Lip/Dox liposomes modified with PBA and coated with Fru can effectively enhance the cytotoxicity of HepG2, reduce the toxicity to normal cells NIH-3T3, and improve the endocytosis of cells to drug-loaded liposomes due to the selective binding of phenylboronic acid and fructose. Therefore, the liposomes co-assembled by DSCP and PBA-PEGSA have good pH response performance and enhance the enrichment ability of liposomes in tumor tissue, which will have good application prospects in the field of tumor therapy. [ABSTRACT FROM AUTHOR]

Plant protein-based adhesives are considered to be the most potential substitutes for petroleum-based adhesives in the wood panel industry, however, the poor water resistance and unsatisfactory mechanical performance limit their large-scale application. Moreover, the development of multifunctional plant protein-based adhesives with high strength, mildew proof, and flame-retardant remains a challenge. Plant fibers have been widely used as the reinforcing phase of polymers, but the smooth surface makes them easy to pull out of the matrix, which greatly reduced the strengthening effect. Herein, the phenylboronic acid-tethered hierarchical rough kenaf fibers were constructed to strengthen soy meal (SM) adhesives while imparting multifunction. The hierarchical rough structures and reactive groups on the surface of kenaf fibers made them form stronger mechanical interlocking and chemical crosslinking with SM matrix, coupled with the entanglement and interpenetration of the fibers with a high aspect ratio, which together endowed the SM adhesive with outstanding water-resistant bonding strength. The wet shear strength of the plywood prepared by the resultant SM adhesive increased by 391.7% to 1.18 MPa, which was far higher than the standard of 0.7 MPa for type II plywood (GB/T 9846-2015) in Chinese standards. Benefiting from the phenylboronic acid component, the resultant SM adhesive exhibited excellent mildew-proof and flame-retardant properties. This biomimetic design of kenaf fibers provides a facile and efficient strategy to develop high-performance and multifunctional bio-adhesives. [ABSTRACT FROM AUTHOR]

With the advantages of good coordination and degradability, chitosan is an ideal polymeric carrier material for heterogeneous catalysts. In this paper, natural polymer chitosan was toughened and modified by blending with polyvinyl alcohol. Then, chitosan-polyvinyl alcohol thin film solid loaded palladium catalytic materials were prepared by reduction method using the excellent coordination properties of chitosan in adsorption of palladium ions. Finally, the catalytic material was applied to the Suzuki coupling reaction of halogenated benzene and phenylboronic acid. The results showed that the catalyst has good substrate tolerance, catalytic activity, and recovery performance.

Boronate affinity materials have been widely studied in separation science, chemical sensing, drug delivery and nanomedicine due to their unique recognition mechanism towards cis-diol-containing biomolecules (cis-diols). In this paper, a new phenylboronic acid (PBA)-functionalized silica particle was prepared by one-pot synthetic strategy based on a PBA-coupled silane reagent, which was synthesized using 1,3,5-benzenetricarboxaldehyde as a spacer arm to covalently link 3-aminophenylboronic acid and 3-aminopropyltriethoxysiliane. Such PBA-functionalized silica particles displayed wrinkle shape with large surface area of 192 m2 g−1, resulting in its high binding capacities of 480 µmol g−1 for catechol and 63 µmol g−1 for adenosine. Moreover, the PBA-functionalized silica particles could rapidly extract the cis-diols in 10 min with a high binding recovery of 83–92%, much higher than its control polymers (1 ~ 47%). In addition to the good extraction performances, the PBA-functionalized silica particles also exhibited fluorescence responses to the cis-diols using two different excitation lights at 300 nm and 470 nm, giving emission lights at 379 nm and 631 nm, respectively, whose fluorescence-responsive mechanism was preliminarily studied. In summary, the developed boronate affinity silica particles can be used not only for the solid-phase extraction of cis-diols, but also to report the recognition events through the fluorescence signals, providing an idea to develop multi-functional boronate affinity materials for simultaneous enrichment and detection of cis-diols in biological samples. [ABSTRACT FROM AUTHOR]

Polymeric nanoparticles with reactive functional groups are an attractive platform for drug carriers that can be conjugated with drugs through a cleavable covalent linkage. Since the required functional groups vary depending on the drug molecule, there is a need for development of a novel post-modification method to introduce different functional groups to polymeric nanoparticles. We recently reported phenylboronic acid (PBA)-containing nanoparticles (BNP) with a unique framboidal morphology created via one-step aqueous dispersion polymerization. Since BNPs have high surface area due to their framboidal morphology and contain a high density of PBA groups, these particles can be used as nanocarriers for drugs that can bind to PBA groups such as curcumin and a catechol-bearing carbon monoxide donor. To further explore the potential of BNPs, in this article we report a novel strategy to introduce different functional groups to BNPs via the palladium-catalyzed Suzuki–Miyaura cross-coupling reaction between the PBA groups and iodo- and bromo-coupling partners. We developed a new catalytic system that efficiently catalyzes Suzuki–Miyaura reactions in water without the need for an organic solvent, as confirmed by NMR. Using this catalyst system, we show that BNPs can be functionalized with carboxylic acids, aldehyde, and hydrazide groups while keeping their original framboidal morphology as confirmed via IR, alizarin red assay, and TEM. Furthermore, the potential of the functionalized BNP in drug delivery applications was demonstrated by conjugating the hydrogen sulfide (H2S)-releasing compound anethole dithiolone to carboxylic acid-functionalized BNPs and show their H2S-releasing capability in cell lysate. [ABSTRACT FROM AUTHOR]

Chemotherapy is the main strategy for inhibiting the tumor growth. However, during the therapy, the side effect of anti-cancer drug will injure normal cells. For reducing the toxic of the free drug, stimuli responsive nanoparticles (NPs) have been prepared base on the pathological acidic environment around tumor for safe and efficient anti-tumor applications. In this study, we fabricated the phenylboronic acid (PBA) modified monomethoxy polyethylene glycol (MEPG) for encapsulating doxorubicin (DOX NPs). In the drug delivery system (DDS), the pH-responsive boric ester could be stable during drug delivery, and enhance DOX rapidly release in tumor lesion under the acidic stimuli. In vitro studies further demonstrated that DOX NPs could efficiently endocytose by tumor cells, and exhibit the similar anti-tumor activity as the free DOX resulting from the pH-responsive drug release profiles under tumor acidic stimuli. In summary, DOX NPs could be a feasible candidate to improve the safe and efficient DOX delivery for improving the potential anti-tumor applications. [ABSTRACT FROM AUTHOR]

During the last decades, palladium nanoparticles (Pd(0) NPs) and Pd(II) compounds were shown to be attractive catalysts for fine organic synthesis. Nanostructured Pd(0) or Pd(II) catalysts have a relatively low environmental impact, but, at the same time, they are indispensable for such processes as Suzuki cross-coupling. This paper describes the preparation of Pd(0) or Pd(II) supported/embedded in hyper-cross-linked polystyrene (HPS) and compares their activity in Suzuki cross-coupling between phenylboronic acid and 4-bromoanisole. Obviously, the palladium charge (Pd(0) ↔ Pd(II)) changes continuously during the reaction catalytic cycle. It would seem that the use of the starting palladium in the form of Pd(0) or Pd(II) should not affect the reaction's kinetic laws for both catalysts, but their special individuality is manifested between them. Nanoparticulate Pd(0) catalysts are stable during the reaction. In contrast, catalysts based on Pd(II) are extremely active in the initial period of the reaction, but then the "hot form" of the catalyst is rapidly converted into the form of Pd(0), whose activity is identical to that of the preliminarily reduced catalyst. This work discusses the possible nature of this phenomenon. A mathematical model for Suzuki cross-coupling reaction was suggested that was able to adequately describe experimental data. The level of reliability (R2) of the correlation between the experimental and calculated data was R2 = 0.97–0.99. [ABSTRACT FROM AUTHOR]

In our study, we designed and developed a glucose biosensor that operates without a battery or chip. This biosensor utilizes the principles of radio frequency (RF) to operate. For the construction of a glucose-sensitive interdigitated capacitor (IDC), a famous glucose-sensitive substance called phenylboronic acid (PBA) is combined with a polyvinyl chloride (PVC) and n,n-dimethylacetamide (DMAC) solution. According to the theory of radio frequency sensing, the resonance frequency shifts whenever there is a change in the capacitance of the glucose-sensitive IDC. This change is caused by the fluctuations in glucose concentrations. As far as we are aware, this is the first glucose sensor that employs the RF principle to detect changes in glucose solution concentrations using PBA as the principal glucose-sensitive material. The sensor can detect glucose levels with remarkable sensitivity, around 40.89 kHz/decade, and a broad dynamic range covering 10 μM to 1 M. Additionally, the designed biosensor has excellent linearity performance, with a value of around 0.988. The proposed glucose biosensor has several benefits: lightweight, inexpensive, easy to build, and an acceptable selectivity response. Our study concludes by comparing the proposed RF sensor’s effectiveness to that of existing glucose sensors, which it outperforms.

Diabetes, characterized by an uncontrolled blood glucose level, is the main cause of blindness, heart attack, stroke, and lower limb amputation. Glucose-sensitive hydrogels able to release hypoglycemic drugs (such as insulin) as a response to the increase of the glucose level are of interest for researchers, considering the large number of diabetes patients in the world (537 million in 2021, reported by the International Diabetes Federation). Considering the current growth, it is estimated that, up to 2045, the number of people with diabetes will increase to 783 million. The present work reviews the recent developments on the hydrogels based on phenylboronic acid and its derivatives, with sensitivity to glucose, which can be suitable candidates for the design of insulin delivery systems. After a brief presentation of the dynamic covalent bonds, the design of glucose-responsive hydrogels, the mechanism by which the hypoglycemic drug release is achieved, and their self-healing capacity are presented and discussed. Finally, the conclusions and the main aspects that should be addressed in future research are shown. [ABSTRACT FROM AUTHOR]

Pd supported on 2-aminoquinoline-7-carboxylic acid functionalized Fe3O4 nanoparticles (Fe3O4-AQCA-Pd) as a new magnetic nanocatalyst was prepared and characterized by ICP-AES, FT-IR, XRD, SEM, TEM, TGA, XRD and EDX techniques. This nanocatalyst is employed for coupling reactions of pyridyl esters with phenylboronic acid to obtain ketone derivatives in good to excellent yields. This green catalyst was easily removed, reused several times with no significant loss of activity and provided a clean synthesis with excellent yield in reduced times. [ABSTRACT FROM AUTHOR]

Introduction: Carbapenemase-producing Enterobacteriales (CPE) are a major health threat worldwide, and therefore the development of rapid detection methods is needed. Here, we established a method to distinguish metallo-β-lactamase and serine carbapenemases using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) with ethylenediaminetetraacetic acid (EDTA) and phenylboronic acid (PB). Methods: To assess the specificity and sensitivity of the method, 110 carbapenemase-producing and 72 carbapenemase-negative Enterobacteriales isolates were collected, among which 51 strains produced only metallo-β-lactamase, 55 strains only serine carbapenemases, and four strains both metallo-β-lactamase and serine carbapenemases. In the proposed MALDI-TOF MS method, imipenem (IPM) and the bacterial strains to be tested were mixed, EDTA and/or PB was added, and the mixture was incubated for 4 h. The carbapenemase type was confirmed by the IPM waveform spectrum before and after incubation. Results: Based on the presence, absence, and recovery of the IPM-cyano-4-hydroxy-cinnamic acid-specific waveform peak near 479 m/z, the detection sensitivity and specificity of the method were 98.2 and 100%, respectively. Discussion: Although CPE detection by MALDI-TOF MS has been studied previously, our method distinguishes between metallo-β-lactamase and serine carbapenemases, which will be very helpful for the clinical selection of antibiotics. [ABSTRACT FROM AUTHOR]

ObjectiveAn online fully automated alkaline hydrolysis method for the determination of chloropropanol esters （MCPDE） and glycidyl esters （GE） in edible oils and fats was developed， and the effects of vegetable oil type and temperature on the conversion of GE to 3-chloro-1，2-propanediol （3-MCPD） were investigated.MethodsBased on the basic principles of AOCS Cd 29c-13， the samples were subjected to hydrolysis， chlorination， liquid-liquid extraction and derivatization on a fully automated sample pretreatment platform， and then separated by a DB-5MS column after injection. The data was determined by multiple reaction monitoring mode （MRM） coupled with the internal standard method.ResultsThe efficiency of GE conversion to 3-MCPDE in the five vegetable oils was significant different. However， the effect of temperature was relatively greater. The alkali hydrolysis time was optimized， and the hydrolysis of MCPDE and GE was basically completed when the hydrolysis was carried out for 7 min at 10℃. The limits of detection for 2-chloro-1，3-propanediol （2-MCPDE）， 3-chloro-1，2-propanediol （3-MCPDE） and GE were all 5 μg/kg calculated by their free forms. There was a good linear relationship between the concentration and ratio of the response ranged from 0 to 0.4 μg/mL. When spiked from 20 to 2 500 μg/kg， the recoveries of MCPDE and GE ranged from 90.3% to 109.7% with the relative standard deviation （n=6） of 1.3%-7.7%， indicating that the precision was better than that of the manual procedure. The method was comparable with the Chinese national standard method for food safety under reviewed and was successfully applied to the determination of FAPAS proficiency test samples.ConclusionThe novel automatic procedure has the advantages of simple operation and high sensitivity， which reduces the labor intensity， improves the detection efficiency and repeatability compared with the reported manual procedure， and can better meet the requirement for quantification of MCPDE and GE in edible oils and fats.

In this study, it is aimed to develop glucose/fructose sensitive poly(ethylene glycol) methyl ether methacrylate (PEGMA) particles which can be employed in controlled drug delivery applications. For this purpose, a boric acid based crosslinker was synthesized using 4-vinylphenylboronic acid and its formation was confirmed by 1H-NMR and FT-IR analyses. Sugar-sensitive polymeric particles were then achieved using this crosslinker and PEGMA monomer in single step and surfactant free emulsion polymerization technique. Polymeric particles were characterized by DLS, SEM, and TEM in terms of size and morphology. In order to determine the sensitivity of the particles to sugar molecules, first Rhodamine B dye (as a model drug) loading experiments were performed. Then, the particles were subjected to glucose/fructose rich media and dye release was monitored as a function of time using UV-Vis spectrophotometry. The results of the current study revealed that the PEGMA particles were more sensitive to fructose (~39% release) compared to glucose (~25% release) at pH 7.4 and 310 K.

To prepare chitosan-loaded nanoparticles (NPs) that enhance the oral bioavailability of puerarin (Pur) and render it responsive to reactive oxygen species (ROS). This research makes substantial progress towards the theory of intelligent drug delivery, offering a new reference for combining Pur with other natural medicinal active ingredients. The acylation reaction between chitosan and ROS-sensitive 3-carboxyphenylboronic acid (PBA) was used to synthesise ROS-sensitive phenylboronylated chitosan (PBACS). Subsequently, PBACS-PBA-Pur-NPs and PBACS-TPP-Pur-NPs were prepared via ion gelation after the addition of PBA and sodium tripolyphosphate(TPP), respectively. The physicochemical and functional properties of both NPs were compared, and their differences were preliminarily studied through molecular docking. Reactive oxygen species-sensitive PBACS was successfully synthesised. Of the two NPs prepared, PBACS-TPP-Pur-NPs had a size of 127.2 ± 0.80 nm, polydispersity index (PDI) of 0.129 ± 0.0008, and an encapsulation rate of 95.75 ± 0.387 %, whereas PBACS-PBA-Pur-NPs had a size of 149.8 ± 0.1414 nm, PDI of 0.389 ± 0.0012, and an encapsulation rate of 91.77 ± 0.279 %. The micromorphology of the PBACS-TPP-Pur-NPs exhibited better physical properties. However, PBACS-PBA-Pur-NPs demonstrated a faster in vitro release and more significant in vitro anti-inflammatory effects. Pharmacokinetically, the AUC 0–24 , T max , and C max of PBACS-PBA-Pur-NPs were 3.485, 2.117, and 3.339 times higher, respectively, than those of Pur. The AUC 0–24 , T max , and C max of PBACS-TPP-Pur-NPs were 2.41, 1.33, and 2.03 times higher, respectively, than those of Pur. Molecular simulation revealed that the binding energy of PBACS-PBA-Pur -NPs was approximately −4.34 kcal/mol and that of PBACS-TPP-Pur-NPs was even lower, approximately −5.93 kcal/mol, suggesting that the NPs prepared with TPP are more densely packed than those designed with PBA, resulting in slower and reduced drug release. The NPs constructed in this study effectively reduced inflammatory factors at the disease site, providing a theoretical and experimental basis for the application of nano drugs in inflammatory disease models. In addition, the molecular docking study of the two NPs offered insights into the relationship between the release and structure of subsequent nano drugs. [Display omitted] [ABSTRACT FROM AUTHOR]

Quantum dots (QDs) have emerged as a prominent nanomaterial, finding diverse applications in semiconductors, optoelectronics, and biomedical detection. This study focuses on synthesizing perovskite QDs through a wet chemical method and subsequently modifying them with phenylboronic acid (PBA) to develop a non-enzymatic glucose sensing device. Structural changes post PBA modification and the glucose reaction mechanism were elucidated using XRD, TEM, and FTIR analyses. Photoluminescence (PL) spectroscopy was employed to monitor luminescence variations of CsPbBr 3 /Cs 4 PbBr 6 @PBA (QD@PBA) across different glucose concentrations. In addition to detecting common glucose concentrations (1–5 mM), QD@PBA can also detect extremely low glucose concentrations. Beyond conventional applications in food and blood glucose monitoring, it has significant potential for metabolic monitoring of cellular microenvironments and related drug development. In cell toxicity assessments, QD@PBA demonstrated no adverse reactions or alterations in cellular morphology following a three-day culture period. Its exceptional excitation efficiency, robust selectivity, and biocompatibility suggest promising applications as a human serum glucose sensor. Moreover, the QD@PBA's high sensitivity and prolonged stability position it favorably for further exploration in studying cellular microenvironments. [Display omitted] • A modified QDs were synthesized as a non-enzymatic glucose sensing device. • QD@PBA has non-cytotoxic reaction after three days of cell culture. • QD@PBA is potential applications for the cellular microenvironment observation. • QD@PBA is potential applications for human blood glucose sensing. [ABSTRACT FROM AUTHOR]

[Display omitted] • Prodrugs PBE-AMF and PBA-AMF are activated by H 2 O 2 to release amonafide (AMF). • AMF's fluorescence and toxicity qualify PBE-AMF and PBA-AMF as theranostic tools. • Cancer cells with the highest H 2 O 2 level are the most sensitive to PBE-AMF. • PBA-AMF surpasses PBE-AMF in stability, solubility, and sialic acid affinity. • PBA-AMF selectively eradicate breast cancer cells with a high H 2 O 2 level. Leveraging the elevated hydrogen peroxide (H 2 O 2) levels in cancer cells, H 2 O 2 -activated prodrugs have emerged as promising candidates for anticancer therapy. Notably, the efficacy of these prodrugs is influenced by the varying H 2 O 2 levels across different cancer cell types. In this context, we have developed a novel H 2 O 2 -activated prodrug, PBE-AMF, which incorporates a phenylboronic ester (PBE) motif. Upon H 2 O 2 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 H 2 O 2 concentration and anticancer activity. The breast cancer cell line MDA-MB-231, characterized by high H 2 O 2 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 H 2 O 2 -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 H 2 O 2 levels, thereby offering new horizons in cancer diagnostics and treatment. [ABSTRACT FROM AUTHOR]

A novel phenylboronic acid and amino bifunctional modified silica gel (SiO2-NH2-FPBA) was prepared, which was 30–80 μm, had a pore size of 8.69 nm, a specific surface area of 206.89 m2/g, was stable at low temperature, and contained 0.4793 mmol/g of the phenylboronic acid group and 1.6377 mmol/g of the amino group. It was used to develop a rapid separation method for phenolic acids. The results showed that it could adsorb 93.64 mg/g caffeic acid, 89.35 mg/g protocatechuic acid and 79.66 mg/g gallic acid. The adsorption process was consistent with the pseudo-second-order model (R2 > 0.99), and fitted the Langmuir isotherm model well (R2 > 0.99). CH3COOH could effectively desorb phenolic acids (>90%) and did not destroy their structures. When SiO2-NH2-FPBA was added to crude extract of Clerodendranthus spicatus, 93.24% of the phenolic acids could be captured, and twenty-two kinds of phenolic acids were identified by Q Exactive HF LC-MS. Furthermore, the isolated phenolic acids from Clerodendranthus spicatus possessed great DPPH, ABTS, and hydroxyl radicals scavenging activities and ferric reducing power. They also demonstrated effective inhibition of α-amylase and α-glucosidase activities (IC50 = 110.63 ± 3.67 μg/mL and 64.76 ± 0.30 μg/mL, respectively). The findings indicate that SiO2-NH2-FPBA has significant potential in practical applications of separating active constituents from natural resources.

Gu Gong,1,* Xiuhui Tang,2,* Jiayuan Zhang,2 Xiao Liang,2 Jiebing Yang,2 Quanshun Li2 1Department of Orthopaedic Surgery, China-Japan Union Hospital, Jilin University, Changchun, 130031, People’s Republic of China; 2Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China*These authors contributed equally to this workCorrespondence: Quanshun Li; Jiebing Yang Tel/Fax +86-431-85155200Email quanshun@jlu.edu.cn; yangjiebing@lntu.edu.cnBackground: The construction of tumor-targeting carriers with favorable transfection efficiency was of great significance to achieve the tumor gene therapy. The phenylboronic acid-modified polyamidoamine (namely PP) was employed as a carrier for the delivery of Polo-like kinase-1 siRNA (siPlk-1), inducing an obvious anti-tumor response.Materials and Methods: The interaction between PP and siPlk-1 was evaluated by gel retardation assay. The transfection efficiency and tumor-targeting ability were analyzed by flow cytometry and confocal laser scanning microscopy, using hepatocarcinoma cell line HepG2 as a model. The anti-proliferation effect of PP/siPlk-1 and related mechanism were studied using the strategies of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, cell apoptosis and cell cycle arrest. The anti-migration effect induced by PP/siPlk-1 delivery was assayed by wound healing and Transwell migration techniques. Finally, quantitative real-time PCR and Western blotting were performed to measure the expression level of Plk-1 and other key targets.Results: The derivative PP could achieve the condensation of siPlk-1 into stable nanoparticles at nitrogen/phosphate groups ratio (N/P ratio) of > 3.0, and it could facilitate the transfection of siPk-1 in a phenylboronic acid-dependent manner. The PP/siPlk-1 nanoparticles exhibited obvious anti-proliferation effect owing to the gene silence of Plk-1, which was identified to be associated with the cell apoptosis and cell cycle arrest at G2 phase. Meanwhile, PP/siPlk-1 transfection could efficiently suppress the migration and invasion of tumor cells.Conclusion: The derivative PP has been demonstrated to be an ideal tumor-targeting carrier for the delivery of Plk-1 siRNA, exhibiting great potential in the gene therapy of malignant tumors.Keywords: phenylboronic acid, polyamidoamine, tumor-targeting ability, siPlk-1, gene therapy

The use of hydrogel-based contact lens materials holds promise for ophthalmic drug delivery by increasing drug residence time, improving drug bioavailability, reducing administration frequency, and enhancing special site targeting. Issues such as ease of manufacturing, lens comfort and appropriate release kinetics must be considered. Furthermore, the high water content of hydrogel materials can result in rapid and poorly controlled release kinetics. Herein, we modified common hydrogels used in contact lens manufacturing with phenylboronic acid (PBA). PBA addresses these material design issues since boronate esters are easily formed when boron acid and diols interact, opening up a pathway for simple modification of the model lens materials with saccharide based wetting agents. The wetting agents have the potential to improve lens comfort. Furthermore, the hydrophobicity of PBA and the presence of diols can be useful to help control drug release kinetics. In this work, polymerizable 3-(acrylamido)phenylboronic acid (APBA) was synthesized and incorporated into various hydrogels used in contact lens applications, including poly(2-hydroxyethylmethacrylate) (PHEMA), polyvinylpyrrolidone (PVP) and poly(N,N-dimethyl acrylamide) (PDMA) using UV induced free radical polymerization. The APBA structure and its incorporation into the hydrogel materials were confirmed by NMR and FTIR. The materials were shown to interact with and bind wetting agents such as hyaluronan (HA) and hydroxypropyl guar (HPG) by simple soaking in an aqueous solution. The equilibrium water content of the modified materials was characterized, demonstrating that most materials are still in the appropriate range after the introduction of the hydrophobic PBA. The release of three model ophthalmic drugs with varying hydrophilicity, atropine, atropine sulfate and dexamethasone, was examined. The presence of PBA in the materials was found to promote sustained drug release due to its hydrophobic nature. The results suggest that the modification of the materials with PBA was able to not only provide a mucoadhesive property that enhanced wetting agent interactions with the materials, but had the potential to alter drug release. Thus, the modification of contact lens materials with mucoadhesive functionality may be useful in the design of hydrogel contact lenses for ophthalmic drug release and wetting agent binding. [ABSTRACT FROM AUTHOR]

Reduction of nonspecific signals (noise) in electrochemical biosensors is important for the realization of enzyme‐free, point‐of‐care (POC) diagnostic devices. In this study, a simple biosensor interface that simultaneously realizes analyte signal enhancement and noise reduction to increase signal‐to‐noise ratio in a field‐effect transistor‐based potentiometric biosensor is proposed. As a proof‐of‐concept, a phytic‐acid‐doped self‐functionalized polyaniline (pAni)‐based nanostructure is designed. It is shown that the incorporation of gold nanoparticles in the nanostructure increases the signal intensity in serotonin sensing. Moreover, the phenylboronic acid moiety in the pAni backbone and porous nanostructure of the pAni nanostructure reduces the interfering noise generated by catecholamines and human serum albumin. It is believed that this study will contribute to the realization of versatile and multiplexed POC diagnostic devices in the future. [ABSTRACT FROM AUTHOR]

The BRCA1 dysfunction and HR deficiency in TNBC are responsible for high effectiveness of DNA-damaging agents in TNBC treatment. Preclinical and clinical studies confirmed the effectiveness of cisplatin in TNBC treatment. Nevertheless, the clinical utility of cisplatin is inadequate due to severe systemic side effects and resistance development. Dual-action cisplatin (IV) prodrugs provide an excellent opportunity to improve anticancer activity, reduce toxicities and minimize chance of resistance development. Therefore, in this investigation we have synthesized cisplatin-chlorambucil (CP-CBL) prodrug and loaded it with venetoclax (VTX) in phenylboronic acid conjugated TPGS-lactide nanoparticles (TNPs) to achieve tumor-targeted drug delivery thereby reducing the therapeutic dose as well as increasing the efficacy of free cisplatin, chlorambucil and venetoclax. The TNPs possessed particle size of 143 nm, PDI 0.186 and entrapment efficiency of 63.5 % and 56.4 % for VTX and CP-CBL. The TNPs followed Higuchi release kinetic model and represented biphasic release behaviour with early burst release of drug within 2 h succeeded by sustained drug release till 72 h. Further, the TNPs showed ∼ 42 folds and ∼ 19 folds reduction in the IC 50 values compared to free CP. Also, higher cellular uptake and therefore greater apoptotic index was observed for the TNPs in comparison to the untargeted nanoparticles. The TNPs further showed higher ROS generating potential, enhanced mitochondrial membrane depolarization, higher intensity of nuclear condensation and highest level of caspase-3 expression. Moreover, a noteworthy decrease in the tumor volume was noticed in the mice treated with TNPs along with lower serum toxicity biomarker levels compared to the free drugs. Overall, the developed TNPs proved to be a promising and safer strategy for inducing triple-hit action in TNBC management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: Oral biofilms, including pathogens such as Porphyromonas gingivalis, are involved in the initiation and progression of various periodontal diseases. However, the treatment of these diseases is hindered by the limited efficacy of many antimicrobial materials in removing biofilms under the harsh conditions of the oral cavity. Our objective is to develop a gel-type antimicrobial agent with optimal physicochemical properties, strong tissue adhesion, prolonged antimicrobial activity, and biocompatibility to serve as an adjunctive treatment for periodontal diseases., Methods: Phenylboronic acid-conjugated alginate (Alg-PBA) was synthesized using a carbodiimide coupling agent. Alg-PBA was then combined with tannic acid (TA) to create an Alg-PBA/TA hydrogel. The composition of the hydrogel was optimized to enhance its mechanical strength and tissue adhesiveness. Additionally, the hydrogel's self-healing ability, erosion and release profile, biocompatibility, and antimicrobial activity against P. gingivalis were thoroughly characterized., Results: The Alg-PBA/TA hydrogels, with a final concentration of 5 wt% TA, exhibited both mechanical properties comparable to conventional Minocycline gel and strong tissue adhesiveness. In contrast, the Minocycline gel demonstrated negligible tissue adhesion. The Alg-PBA/TA hydrogel also retained its rheological properties under repeated 5 kPa stress owing to its self-healing capability, whereas the Minocycline gel showed irreversible changes in rheology after just one stress cycle. Additionally, Alg-PBA/TA hydrogels displayed a sustained erosion and TA release profile with minimal impact on the surrounding pH. Additionally, the hydrogels exhibited potent antimicrobial activity against P. gingivalis, effectively eliminating its biofilm without compromising the viability of MG-63 cells., Significance: The Alg-PBA/TA hydrogel demonstrates an optimal combination of mechanical strength, self-healing ability, tissue adhesiveness, excellent biocompatibility, and sustained antimicrobial activity against P. gingivalis. These attributes make it superior to conventional Minocycline gel. Thus, the Alg-PBA/TA hydrogel is a promising antiseptic candidate for adjunctive treatment of various periodontal diseases., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

A new probe, 4-(((3',6'-bis(diethylamino)-3-oxospiro[isoindoline-1,9'-xanthen]-2-yl)imino)methyl)phenyl)boronic acid (R4B) was prepared by facile condensation of 4-formylphenylboronic acid and rhodamine B hydrazide. R4B was characterized by spectroscopic methods and single crystal X-ray diffraction. The sensor R4B solution turned pink and emitted orange fluorescence only in the presence of sialic acid but remained colorless and non-fluorescent otherwise. The sugar recognition performance was investigated via UV-vis and fluorescence spectroscopic studies. Our results revealed that R4B has good affinity and selectivity for sialic acid over common monosaccharides, with a detection limit as low as 10 -7 M. Furthermore, R4B selectively inhibited growth of human colorectal adenocarcinoma HT-29 (IC 50 <20 µM) without significant cytotoxicity to normal human colon fibroblasts CCD-18Co. Treatment with R4B suppressed HT-29 colony formation via mitochondrial apoptosis in a time-dependent manner. Cellular imaging studies also revealed the ability of R4B as a fluorescence dye to detect intracellular sialic acid and showed mitochondria-tracking ability in HT-29 cells. In summary, R4B is a potential theranostic for the detection of intracellular sialic acid during the early incubation period, followed by induction of cancer apoptotic cell death at a later treatment point., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)