Phenylboric Acid Research Articles

Preservation of cardiac functions post myocardial infarction in vivo by a phenylboric acid-grafted hyaluronic hydrogel with anti-oxidation and accelerated degradation under oxidative microenvironment

Excessive oxidative stress and inflammatory responses can exacerbate the pathological conditions of left ventricular (LV) myocardium and even lead to heart failure post myocardial infarction (MI). Intramyocardial injectable antioxidative hydrogels without loading of any cells, genes or cell growth factors are attractive for the translation in clinical therapy. In this study, a self-adaptive, degradable and antioxidative hydrogel (R gel) was prepared by a Schiff base reaction between adipic acid dihydrazide (ADH)-modified and phenylboric acid (PBA)-grafted hyaluronic acid (HA-ADH-PBA) and oxidized dextran (Ox-Dex) with aldehyde groups. Compared to the non-reactive control hydrogel (N-R gel), the R gel exhibited high efficiency in scavenging excessive ROS in vitro and in vivo, and protected cells from oxidative damage in infarcted rat myocardium in vivo, as demonstrated by significantly reduced cell membrane peroxidation and apoptosis, suppressed inflammation, preserved cardiac functions, and promoted LV vascularization. The expressions of key genes associated with the inflammation in short term (3 d) and cardiomyocyte functions in long term (8 w) were investigated to explore the mechanisms in a molecular level.

Injectable multifunctional hyaluronic acid/methylcellulose hydrogels for chronic wounds repairing

Herein, an injectable multifunctional hydrogel based on dopamine grafted hyaluronic acid and phenylboric acid grafted methylcellulose was fabricated for promoting the repair of diabetic wounds. The prepared hydrogel possessed multifunctional properties including rapid gelation time (less than 10 s), self-healing, high water absorbency, tissue adhesiveness and excellent antioxidant activity. After loading Ag nanoparticles and the recombinant humanized collagen type III with high affinity to cells, the hydrogel exhibited properties of pH-/H2O2-responsive drug release profile, promoting cell proliferation and ideal antibacterial activity. Moreover, the in vivo experimental results demonstrated the prepared hydrogel could significantly accelerate wound repair by enhancing the collagen deposition and granulation tissue regeneration, reducing the expression of CD68 and improving the production of Ki67 and CD31 simultaneously. In conclusion, these multifunctional injectable hydrogels possessed great potential in chronic wound dressings.

Assembling Microgels via Dynamic Cross-Linking Reaction Improves Printability, Microporosity, Tissue-Adhesion, and Self-Healing of Microgel Bioink for Extrusion Bioprinting.

Extrusion bioprinting has been widely used to fabricate complicated and heterogeneous constructs for tissue engineering and regenerative medicine. Despite the remarkable progress acquired so far, the exploration of qualified bioinks is still challenging, mainly due to the conflicting requirements on the printability/shape-fidelity and cell viability. Herein, a new strategy is proposed to formulate a dynamic cross-linked microgel assembly (DC-MA) bioink, which can achieve both high printability/shape-fidelity and high cell viability by strengthening intermicrogel interactions through dynamic covalent bonds while still maintaining the relatively low mechanical modulus of microgels. As a proof-of-concept, microgels are prepared by cross-linking hyaluronic acid modified with methacrylate and phenylboric acid groups (HAMA-PBA) and methacrylated gelatin (GelMA) via droplet-based microfluidics, followed by assembling into DC-MA bioink with a dynamic cross-linker (dopamine-modified hyaluronic acid, HA-DA). As a result, 2D and 3D constructs with high shape-fidelity can be printed without post-treatment, and the encapsulated L929 cells exhibit high cell viability after extrusion. Moreover, the addition of the dynamic cross-linker (HA-DA) also improves the microporosity, tissue-adhesion, and self-healing of the DC-MA bioink, which is very beneficial for tissue engineering and regenerative medicine applications including wound healing. We believe the present work sheds a new light on designing new bioinks for extrusion bioprinting.

Simultaneous determination of monochloropropanediol esters and glycidyl esters in vegetable oils by acidic transesterification-gas chromatography-mass spectrometry

建立了一种气相色谱-质谱同时测定植物油中3-氯丙二醇酯、2-氯丙二醇酯和缩水甘油酯的方法。称取0.25 g样品,依次加入内标工作液、四氢呋喃和酸性溴化钠溶液,50 ℃水浴反应15 min,加入6 g/L碳酸氢钠溶液终止反应,使用正己烷提取,上层液经氮气吹干后用四氢呋喃溶解。随后加入1.8%(v/v)硫酸-甲醇溶液于40 ℃恒温水浴中反应16 h,加入饱和碳酸氢钠溶液终止反应。样液再经过净化、衍生、提取、氮吹后,以1 mL正己烷定容,过膜,进样测定。采用毛细管气相色谱柱DB-5MS(30 m×0.25 mm×1 μm)分离,程序升温,电子轰击电离(EI)源检测,在选择离子扫描模式下,以保留时间和特征离子信息进行定性分析,内标法定量。结果表明,3-氯丙二醇酯、2-氯丙二醇酯和缩水甘油酯在0.01~0.80 mg/L范围内线性关系良好,相关系数(r2)均在0.999以上,方法的检出限(S/N=3)和定量限(S/N=10)分别为25、25、20 μg/kg和75、75、60 μg/kg。选取4种不同基质类型的样品,在低、中、高3个不同添加水平下的平均回收率为89.0%~98.7%,相对标准偏差(RSD)在2.05%~7.81%之间。采用该方法测定了市售112份植物油样本,其中有84份样本检出3-氯丙二醇酯、2-氯丙二醇酯和缩水甘油酯。与已建立的国家标准方法(GB 5009.191-2016)和行业标准方法(SN/T 5220-2019)相比,该方法所采用的酸性酯交换法可避免副反应(碱性条件下3-氯丙二醇、2-氯丙二醇及3-溴丙二醇向游离态缩水甘油转化)的发生,同时该方法也弥补了国家标准和行业标准无法对3-氯丙二醇酯、2-氯丙二醇酯和缩水甘油酯同时进行测定的缺失。该方法实验操作更高效,结果更准确、重复性更好,对我国植物油中3-氯丙二醇酯、2-氯丙二醇酯和缩水甘油酯污染水平的控制、检测标准的制定和生产工艺的优化具有一定的理论和现实意义。

Glucose and MMP-9 dual-responsive hydrogel with temperature sensitive self-adaptive shape and controlled drug release accelerates diabetic wound healing.

Chronic diabetic wounds are an important healthcare challenge. High concentration glucose, high level of matrix metalloproteinase-9 (MMP-9), and long-term inflammation constitute the special wound environment of diabetic wounds. Tissue necrosis aggravates the formation of irregular wounds. All the above factors hinder the healing of chronic diabetic wounds. To solve these issues, a glucose and MMP-9 dual-response temperature-sensitive shape self-adaptive hydrogel (CBP/GMs@Cel&INS) was designed and constructed with polyvinyl alcohol (PVA) and chitosan grafted with phenylboric acid (CS-BA) by encapsulating insulin (INS) and gelatin microspheres containing celecoxib (GMs@Cel). Temperature-sensitive self-adaptive CBP/GMs@Cel&INS provides a new way to balance the fluid-like mobility (self-adapt to deep wounds quickly, approximately 37 °C) and solid-like elasticity (protect wounds against external forces, approximately 25 °C) of self-adaptive hydrogels, while simultaneously releasing insulin and celecoxib on-demand in the environment of high-level glucose and MMP-9. Moreover, CBP/GMs@Cel&INS exhibits remodeling and self-healing properties, enhanced adhesion strength (39.65 ± 6.58 kPa), down-regulates MMP-9, and promotes cell proliferation, migration, and glucose consumption. In diabetic full-thickness skin defect models, CBP/GMs@Cel&INS significantly alleviates inflammation and regulates the local high-level glucose and MMP-9 in the wounds, and promotes wound healing effectively through the synergistic effect of temperature-sensitive shape-adaptive character and the dual-responsive system.

Novel multifunctional dual-dynamic-bonds crosslinked hydrogels for multi-strategy therapy of MRSA-infected wounds

Wound healing is a complex dynamic process involving hemostasis, inflammation, proliferation and remodeling stages. It is urgent need to develop multifunctional hydrogels to treat multiple links of wound healing. In this work, we designed novel multifunctional dual-dynamic-bonds crosslinked hydrogels through the electrostatic interaction between phenylboric acid and the amino group of chitosan, and the dynamic borate ester bond between phenylboric acid and the catechol structure of PDA-modified CNTs. This dual dynamic cross-linking mechanism endowed hydrogels with very fast self-healing properties, which could quickly form a whole dressing after being injected into the wound site. The phenylboric acid and catechol structures endowed hydrogels with excellent adhesion properties, the adhesion strength to pig skin was up to 27.6 kPa, could be used for hemostasis in vivo. Moreover, hydrogels displayed the advantages of injectable, rapid shape adaptation, antioxidant, biocompatibility, blood compatibility, electrical conductivity and photothermal antibacterial properties. In the MRSA-infected wound model, hydrogels could effectively reduce the expression level of wound inflammatory factors, accelerate collagen deposition, epithelial tissue and vascular regeneration, and thus promote wound healing. This work provides a new idea for the design of multi-strategy therapy for wound healing and has broad clinical application prospects.

Surface modification of MCM-41 by chain transfer free radical polymerization and their utilization for intracellular pH-responsive delivery of curcumin

In this paper, a simple method that relied on direct chain transfer free radical polymerization was reported to synthesize MSNs based polymeric composites (named as MCM-41-SH-poly (PEGMA-co-VPA)) using poly (ethylene glycol) monomethyl ether (PEGMA) and 4-vinyl phenylboric acid (VPA) as monomers. The utilization of MCM-41-SH-poly (PEGMA-co-VPA) to load and delivery curcumin (CUR) was also evaluated in detail. The structure, properties, drug loading and release behaviors were evidenced by various characterization techniques. The results from biological studies have shown that CUR can be effectively loaded on MCM-41-SH-poly (PEGMA-co-VPA) with high drug loading rate through formation of borate bond between CUR and VPA. More importantly, resultant drug-loading complexes displayed excellent water dispersibility and CUR could be released from complexes with pH responsiveness. Taken together, we have developed a simple method for surface modification MCM-41 and resultant composites could display improved properties for intracellular controlled drug delivery applications.

Enhanced photocatalytic driven hydroxylation of phenylboric acid to phenol over pyrenetetrasulfonic acid intercalated ZnAl-LDHs

Layered double hydroxides (LDHs) own admirable potential due to their controllable composition and exchangeable interlayer anions. Herein, pyrenetetrasulfonic acid (PTS) intercalated ZnAl-LDHs (denoted as ZnAl-xPTS, x represents the amount of NaPTS in the starting material) are synthesized by a co-precipitation method, which display enhanced photocatalytic activity towards the hydroxylation of phenylboric acid to phenol. Various characterizations suggest that PTS plays significant roles in improving the photocatalytic activity: (1) PTS extends the light absorption from ultraviolet to visible light region; (2) the introduction of PTS upshifts the conduction band, which is feasible for the formation of O2∙-; (3) ZnAl-xPTS produces more free electrons under light irradiation, which leads to greatly improved activity. This study develops an alternative LDHs based photocatalyst for the production of phenol, which also provides an efficient strategy to improve the photocatalytic activity of LDHs.

Preparation and roles of sliver-loaded viscous hydrogel in healing of full-thickness skin defect wounds with bacterial colonization in mice

Preparation and roles of sliver-loaded viscous hydrogel in healing of full-thickness skin defect wounds with bacterial colonization in mice

Conductive, Self-Healing, Adhesive, and Antibacterial Hydrogels Based on Lignin/Cellulose for Rapid MRSA-Infected Wound Repairing.

The abuse of antibiotics induces the emergence of drug-resistant bacteria, which greatly increases the difficulty of clinical treatment of infected wounds. It is urgent to design a multifunctional wound dressing independent of antibiotics. In this work, we designed multifunctional hydrogels based on lignin and cellulose in natural polymers. Lignin with antioxidant properties could reduce silver nanoparticles in situ and could also be used as a crosslinking agent to construct hydrogels between hydroxypropyl cellulose modified with phenylboric acid by a dynamic borate bond. Hydrogels have excellent properties such as self-healing, shape adaptability, biocompatibility, blood compatibility, antioxidant properties, excellent broad-spectrum antimicrobial properties, good tissue adhesion, and electrical conductivity. The tissue adhesion of hydrogels endows them with an excellent hemostasis property in a rat liver injury model. In vivo experiments demonstrated that hydrogels can maintain a moist healing environment, reduce inflammatory cell infiltration, promote M2 macrophage polarization, accelerate collagen deposition, promote the regeneration of new blood vessels, and significantly speed up the wound healing of methicillin-resistant Staphylococcus aureus (MRSA)-infected wounds. Therefore, these multifunctional hydrogels are an excellent candidate to treat multiple stages of wound healing and have a broad application prospect in the medical field.

Preparation of heat resistant boron-containing phenyl silicone oil and its initial degradation mechanism in air

Boron-containing phenyl silicone oil (BCPSO) with terminal boronic hydroxyl groups was synthesized by acid-catalyzed balance condensation polymerization using phenylboric acid, dimethyldichlorosilane and diphenyldichlorosilane as raw materials. The structure of BCPSO was characterized by 1H, 13C and 29Si nuclear magnetic resonance (NMR) and Fourier transform infrared spectrometry (FTIR). The thermal degradation behavior of BCPSO was tested by thermogravimetry-Fourier transform infrared spectrometry (TG-FTIR) analysis. The TG-FTIR results indicated that thermal decomposition of BCPSO had significant hysteresis over that of phenyl silicone oil. The empty electron orbital of boron atom could accept electron of peroxide free radical to generate conjugation effect at initial degradation stage of BCPSO, and this phenomenon was confirmed by 11B NMR, FTIR and Raman spectroscopies. As a result, temporarily stable intermediate was formed which increased the heat resistant of BCPSO.

Boronate affinity imprinted hydrogel sorbent from biphasic synergistic high internal phase emulsions reactor for specific enrichment of Luteolin

The dynamic coexistence of heterostructures is crucial for the synergistic function of molecularly imprinted polymers (MIPs) derived from high internal phase emulsions (HIPEs). In this work, hydrophilic boronate affinity imprinted hydrogel sorbents (H-UIO-66-NH2-IHIPEs) were prepared by biphasic synergistic HIPEs droplet reactors filled with reactive microencapsulation system, and used to capture and separate cis-diol containing luteolin (LTL) from complex extraction samples with high selectivity. As the main solid emulsifier, UiO-66-NH2, prototype zirconium-based metal–organic frameworks (MOFs) greatly improves the mechanical performance of the hydrogel, whilst preventing overuse of surfactants. Space-confined formation of imprinted sites in the external phase is realized in the presence of hydrophilic acrylamide phenylboric acid monomer (H-BA), which endows the specific affinity with pH responsiveness to LTL. In addition, the filled microinclusion compound containing elastic monomer octadecyl methacrylate (SMA) and functional monomer glycidyl methacrylate (GMA) simultaneously added interfacial cross-linking reaction to provide stable pore volume and pore shape. Combined with these excellent properties, H-UIO-66-NH2-IHIPEs showed fast capture kinetics (75 min) and large uptake amount (39.77 mg g−1) at 298 K, and confirmed the existence of a uniform chemisorption monolayer. Moreover, excellent recyclability of 6.24% loss in adsorption amount after five adsorption–desorption cycles was observed. Finally, the LTL content of the purified product (about 97.38%) was higher than that of the crude extract (about 85.0%). This study sheds a new light for the design of novel imprinted hydrogel sorbents combined with binary synergistic components.

A sequentially responsive nanogel via Pt(IV) crosslinking for overcoming GSH-mediated platinum resistance

Chemotherapy efficiency of platinum(II) (Pt(II)) is often attenuated owing to the low intracellular drugs concentration and glutathione (GSH)-mediated detoxification. To address these problems, we fabricated a step-by-step responsive nanogel (~160 nm) by copolymerization between four functional monomers. Hydrophilic methoxypolyethylene glycols (mPEG) distributedrandomly on the surface of particles endowed the nanogel with “stealth” property in blood circulation, while the chemical crosslinking inside particles by platinum(IV) (Pt(IV)) linker remarkably increased the stability of nanogel in vivo. These advantages of nanogels leaded to higher accumulation at tumor region (6.4% ID/g), followed by triggering the dePEGylation effect by the cleavage of ortho ester at tumoral extracellular pH. Meanwhile, the exposed phenylboric acid (PBA) could significantly increase cellular uptake and intracellular drugs levels by targteing sialic acid residues on the cells membrane. More importantly, this nanogels could further deplete intracellular glutathione (GSH) by the dual-regulation of platinum(IV) and arylboronic ester, resulting in enhanced platinum(II) toxicity both in vitro and in vivo, eventually achieving superior inhibition rate (79.14%) in A549/DDP tumor. Thus, the sequentially responsive nanogel could be considered as an effective strategy for cancer treatment.

Stabilizing Formamidinium Lead Iodide Perovskite Precursor Solution with Phenylboric Acid

The instability of the perovskite precursor solution seriously affects the purity of the perovskite films, which is one of the key factors for the low reproducibility for highly efficient devices. Formamidinium‐based perovskite with more suitable spectral absorption range and higher thermal stability has become the mainstream material. However, the side reactions in pure formamidinium lead iodide solution have not been fully revealed. Herein, it is demonstrated that self‐condensation of formamidinium iodide occurs to form the by‐product s‐triazine, and its content increases with the aging time of the solution. It is also discovered that phenylboric acid (PBA) can effectively inhibit the self‐condensation reaction and the content of the s‐triazine is decreased by more than 95% in the solution aging at 60 °C for 7 days. The PBA used as the stabilizer not only enhances purity and decreases defect density of the perovskite films but also strongly enhances the reproducibility for highly efficient perovskite solar cells.

Polymers Based on Phenyl Boric Acid in Tumor-Targeted Therapy.

Tumors are still among the major challenges to human health. Tumor-targeted therapy is an effective way to treat tumors based on precise medical models. Sialic acid (SA) is overexpressed on the surface of tumor cells, and Phenyl Boric Acid (PBA) can specifically bind to SA. However, studies on the use of PBA in tumor-targeted therapy are few. To summarize and analyze the characteristics and influencing factors of tumor targeted therapy in recent years, and the influencing factors of phenyl boric acid modified polymers in tumor targeted therapy, such as hydrogen ion concentration (pH), Adenosine Triphosphate (ATP), and sugars. This paper describes the application of phenyl boric acid partially functionalized nano-polymers in various types of targeted tumors, such as breast cancer, lung adenocarcinoma, liver cancer, and so forth. In order to further improve the basic research and clinical workers' understanding of nano-preparations and tumor targeted therapy. At the same time, it is also expected to promote the development value of phenyl boric acid. The findings on tumor-targeted therapy and the role of partially functionalized polymers with PBA in different tumors at home and abroad has been analyzed and summarized in recent years. Tumor-targeted therapy is a promising treatment for tumors. PBA promotes the treatment of tumors using SA, which is highly expressed on the surface of tumor cells. Tumor-targeted therapy has shown great prospects for clinical application in recent years. PBA is beneficial as a member of the drug loading system. Further studies are still needed to promote its development and application.

Novel paper- and fiber optic-based fluorescent sensor for glucose detection using aniline-functionalized graphene quantum dots

Aniline functionalized graphene quantum dots (a-GQDs) is synthesized by microwave-assisted pyrolysis of fructose. After a-GQDs are modulated using phenyl boric acid (PBA), resulting in fluorescence quenching, the a-GQDs/PBA system are employed as a fluorescent turn-on sensor for the glucose detection by the specific reaction of PBA with glucose. The prepared fluorescent sensor using a-GQDs/PBA exhibits high sensitivity and selectivity toward glucose. In addition, the paper-based fluorescent sensor is prepared for portable sensing devices by printing the a-GQDs ink with a commercial inkjet printer, demonstrating a superior visual glucose detection and a good sensitive performance for the detection of glucose in a blood serum and tear samples. Furthermore, the a-GQDs/hydrogel film is evaluated for a wearable sensor as well as fiber optic-based sensor for highly sensitive and fast on-site glucose detection. The prepared fiber optic sensor exhibits remarkable glucose sensing performance with a fast response, a low detection limit of 2.1 μM and excellent recyclability. Finally, the a-GQD/PBA system exhibits excellent biocompatibility and was applied to detect glucose in HeLa cells with satisfactory results. These results provide a novel approach for developing low-cost and flexible sensors for the portable and visual detection of glucose with high sensitivity and selectivity.

Self-assembly system based on water-soluble perylene diimide for sensitive detection and discrimination of tea polyphenols

Tea polyphenols have become one of the promising healthcare molecules due to their anti-cancer, anti-oxidant, and anti-obesity capacities, making tea among the most popular and functional beverages worldwide. However, the sensitive and simple detection and discrimination of tea polyphenols is difficult to achieve since the analogues usually have similar chemical structures with polyhydroxy. Herein, a self-assembly system based on a cationic perylene diimide molecule tagging with phenylboric acid group (PDI-PBA) was constructed for detection and discrimination of catechin molecules (Epicatechin, Epicatechin gallate, Epigallocatechin, Epigallocatechin gallate), a subgroup of tea polyphenols. PDI-PBA could recognize tea polyphenols by dynamic borate ester bonds between PBA groups on PDI-PBA and cis-diols on tea polyphenols. Moreover, the fluorescence quench ratios of PDI-PBA were determined by the different aggregation degrees induced by every tea polyphenol with the unique chemical structure, especially cis-diol numbers. Thus, the selective discrimination could be easily realized by linear discriminant analysis (LDA). The developed system relies mainly on dynamic borate ester bonds between the probe and substrates, the self-assembly of PDI-PBA, and polyhydroxy characteristic of tea polyphenols. This work provides a new strategy for sensitive detection and discrimination of tea polyphenols.

Galactose-based polymer-containing phenylboronic acid as carriers for insulin delivery

The galactose-based polymer is a promising drug delivery material. Herein, a new galactose-based block copolymer, termed as 6-O-vinyl sebacic acid-D-galactopyranosyl ester block 3-acrylamide phenylboric acid p(OVNG-b-AAPBA) was successfully synthesized by ‘block copolymer’ method. The structure of p(OVNG-b-AAPBA) was proved by nuclear magnetic hydrogen spectrum (1 HNMR) and infrared (IR), the thermal stability was observed by thermogravimetric analyzer, and the molecular weights (Mw and Mn) were demonstrated by Gel permeation chromatography (GPC). The above test results suggested that the polymer of p(OVNG-b-AAPBA) was successfully synthesized, and it had optimal molecular weight and thermal stability, which could be used for investigating the drug delivery system. Then, this block copolymer was prepared to the nanoparticle (NP), these NPs had a satisfactory morphology, and their safety was verified by MTT and chronic animal toxicology test. In addition, insulin was encapsulated by the p(OVNG-b-AAPBA) NPs, the drug loading rate and encapsulation efficiency increased with that of AAPBA in the polymer. Finally, this study confirmed that these NPs can effectively maintain the blood sugar of diabetic mice at 96 h. In conclusion, the current study suggested that the insulin-loaded galactose-based polymer-block-3-acrylamide phenylboric acid NPs had slow-release/glucose-responsive drug release performance, which might play an active role in the diabetes therapy.

A near-infrared fluorescent probe based on boric acid hydrolysis for hydrogen peroxide detection and imaging in HeLa cells.

Using the characteristics of hydrogen peroxide that are able to cleave phenyl-boric acid selectively and efficiently, we here report a dicyanoisophorone-boric acid (DCP-BA)-based near-infrared (NIR) fluorescent probe for detection of hydrogen peroxide. This probe shows a rapid, highly selective, and sensitive detection process for hydrogen peroxide with a significant NIR fluorescent turn-on response that has been successfully applied to detect exogenous hydrogen peroxide in HeLa cells.

Non-close packed photonic crystal hydrogel for glucose detection

Based on the importance of fast and non-invasive detection technology of glucose monitoring, a glucose sensor based photonic crystal hydrogel material was prepared. The phenylboric acid was the glucose recognition molecule and the three-dimensional non-close packed array was the signal transformation structure. The experimental results show that the recognition behavior of the hydrogel is shown in the form of diffraction wavelength. As the glucose concentration increases from 0 mol/L to 50 mM, the blue shift of the diffraction wavelength occurs at 10 nm, showing a good sensing property.