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1.
Mikrochim Acta ; 191(7): 432, 2024 06 29.
Article in English | MEDLINE | ID: mdl-38951266

ABSTRACT

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


Subject(s)
Arginine , Biomarkers , Boronic Acids , Cystinuria , Fluorescent Dyes , Limit of Detection , Metal-Organic Frameworks , Humans , Cystinuria/diagnosis , Cystinuria/urine , Metal-Organic Frameworks/chemistry , Fluorescent Dyes/chemistry , Arginine/chemistry , Arginine/blood , Biomarkers/urine , Biomarkers/blood , Boronic Acids/chemistry , Spectrometry, Fluorescence/methods , Zirconium/chemistry
2.
Mikrochim Acta ; 191(8): 444, 2024 07 03.
Article in English | MEDLINE | ID: mdl-38955823

ABSTRACT

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


Subject(s)
Biosensing Techniques , Boronic Acids , Gold , Spectrum Analysis, Raman , Boronic Acids/chemistry , Biosensing Techniques/methods , Gold/chemistry , Humans , Spectrum Analysis, Raman/methods , Silver/chemistry , Metal Nanoparticles/chemistry , Limit of Detection , Transferrin/analysis , Transferrin/chemistry , Molecular Imprinting , Molecularly Imprinted Polymers/chemistry , Glycoproteins/blood , Glycoproteins/chemistry , Biomimetic Materials/chemistry , Dopamine/blood , Dopamine/analysis , Sulfhydryl Compounds
3.
Bioorg Med Chem ; 109: 117790, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-38906067

ABSTRACT

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


Subject(s)
Boronic Acids , Cryoelectron Microscopy , Proteasome Endopeptidase Complex , Proteasome Inhibitors , Proteasome Endopeptidase Complex/metabolism , Proteasome Endopeptidase Complex/chemistry , Animals , Proteasome Inhibitors/pharmacology , Proteasome Inhibitors/chemistry , Proteasome Inhibitors/chemical synthesis , Mice , Boronic Acids/chemistry , Boronic Acids/pharmacology , Boronic Acids/chemical synthesis , Humans , Structure-Activity Relationship , Cysteine Endopeptidases/metabolism , Molecular Structure , Molecular Dynamics Simulation , Drug Discovery
4.
J Am Chem Soc ; 146(25): 17211-17219, 2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38864331

ABSTRACT

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


Subject(s)
Boronic Acids , Polymers , Boronic Acids/chemistry , Polymers/chemistry , Humans , Gene Transfer Techniques , DNA/chemistry , Genetic Vectors/chemistry , Molecular Structure
5.
Chem Commun (Camb) ; 60(52): 6683-6686, 2024 Jun 25.
Article in English | MEDLINE | ID: mdl-38860957

ABSTRACT

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


Subject(s)
Boronic Acids , Curcumin , Esters , Polymers , Reactive Oxygen Species , Reactive Oxygen Species/metabolism , Esters/chemistry , Esters/pharmacology , Humans , Boronic Acids/chemistry , Curcumin/chemistry , Curcumin/pharmacology , Polymers/chemistry , Micelles , Hydrophobic and Hydrophilic Interactions , Antioxidants/chemistry , Antioxidants/pharmacology , Drug Carriers/chemistry , Surface-Active Agents/chemistry , Surface-Active Agents/chemical synthesis , Drug Liberation , Drug Delivery Systems , Cell Survival/drug effects , Molecular Structure
6.
J Control Release ; 371: 570-587, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38852624

ABSTRACT

Myocardial infarction (MI)-induced impaired cardiomyocyte (CM) mitochondrial function and microenvironmental inflammatory cascades severely accelerate the progression of heart failure for compromised myocardial repair. Modulation of the crosstalk between CM mitochondrial DNA (mtDNA) and STING has been recently identified as a robust strategy in enhancing MI treatment, but remains seldom explored. To develop a novel approach that can address persistent myocardial injury using this crosstalk, we report herein construction of a biomimetic hydrogel system, Rb1/PDA-hydrogel comprised of ginsenoside Rb1/polydopamine nanoparticles (Rb1/PDA NPs)-loaded carboxylated chitosan, 4-arm-PEG-phenylboronic acid (4-arm-PEG-PBA), and 4-arm-PEG-dopamine (4-arm-PEG-DA) crosslinked networks. An optimized hydrogel formulation presents not only desired adhesion properties to the surface of the myocardium, but also adaptability for deep myocardial injection, resulting in ROS scavenging, CM mitochondrial function protection, M1 macrophage polarization inhibition through the STING pathway, and angiogenesis promotion via an internal-external spatial combination. The enhanced therapeutic efficiency is supported by the histological analysis of the infarcted area, which shows that the fibrotic area of the MI rats decreases from 58.4% to 5.5%, the thickness of the left ventricular wall increases by 1-fold, and almost complete recovery of cardiac function after 28 days of treatment. Overall, this study reported the first use of a strong adhesive and injectable hydrogel with mtDNA and STING signaling characteristics for enhanced MI treatment via an internal-external spatial combination strategy.


Subject(s)
DNA, Mitochondrial , Hydrogels , Myocardial Infarction , Myocytes, Cardiac , Polymers , Animals , Myocardial Infarction/drug therapy , Myocardial Infarction/metabolism , Hydrogels/administration & dosage , Hydrogels/chemistry , Myocytes, Cardiac/drug effects , Myocytes, Cardiac/metabolism , Male , Polymers/chemistry , Polymers/administration & dosage , Indoles/administration & dosage , Indoles/chemistry , Nanoparticles/administration & dosage , Nanoparticles/chemistry , Chitosan/chemistry , Chitosan/administration & dosage , Rats, Sprague-Dawley , Polyethylene Glycols/chemistry , Polyethylene Glycols/administration & dosage , Rats , Membrane Proteins , Reactive Oxygen Species/metabolism , Boronic Acids , Ginsenosides
7.
Microbiol Spectr ; 12(7): e0008424, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38842354

ABSTRACT

Non-tuberculosis mycobacteria (NTM), particularly Mycobacterium abscessus subsp. abscessus (M. abscessus), are increasingly being recognized as etiological agents of NTM pulmonary disease. However, treatment options for M. abscessus are limited owing to their natural resistance to most antibiotics, including ß-lactams. M. abscessus produces a class A ß-lactamase, whose activity is inhibited by cyclic boronic acid ß-lactamase inhibitors. We aimed to evaluate the in vitro effects of xeruborbactam, a cyclic boronic acid ß-lactamase inhibitor, against M. abscessus when combined with five ß-lactams (amoxicillin, tebipenem, cefdinir, cefuroxime, and cefoxitin). The drug susceptibilities of 43 M. abscessus clinical isolates obtained from 43 patients between August 2005 and May 2014 were tested. The MIC results for each ß-lactam with or without 4 µg/mL xeruborbactam were examined. Xeruborbactam lowered the MIC90 values of tebipenem, amoxicillin, cefuroxime, and cefdinir by 5, ≥4, 3, and 3 dilutions, respectively. The MIC90 values of cefoxitin without xeruborbactam were 32 µg/mL and did not change upon the addition of xeruborbactam. The lowest MIC90 value was obtained for tebipenem with xeruborbactam. Almost all isolates had an MIC of 4 µg/mL; one isolate had an MIC of 2 µg/mL. With respect to the susceptibility to the same family drug, the number of susceptible isolates increased from 1/43 (2%) to 43/43 (100%) for tebipenem with xeruborbactam. Combining tebipenem and xeruborbactam could be considered an effective all-oral regimen that benefits outpatient treatment of M. abscessus pulmonary disease. IMPORTANCE: Mycobacterium abscessus subsp. abscessus (M. abscessus) disease is treated in two phases; injectable drugs for initial followed by others for continuation. There is a need to develop all-oral treatment methods for M. abscessus infection, especially in the continuation phase. However, treatment options for M. abscessus are limited owing to their natural resistance to most antibiotics. This is the first report to evaluate the in vitro effects of xeruborbactam, a cyclic boronic acid ß-lactamase inhibitor capable of inhibiting the class A ß-lactamase produced by M. abscessus, against 43 M. abscessus clinical isolates when combined with five ß-lactam antibiotics. Xeruborbactam lowered the MIC90 values of tebipenem by five dilutions, and the number of susceptible isolates increased from 1/43 (2%) to 43/43 (100%). We showed that the tebipenem-xeruborbactam combination might be of interest to explore further as a potentially effective oral regimen for outpatient treatment of M. abscessus pulmonary disease.


Subject(s)
Anti-Bacterial Agents , Microbial Sensitivity Tests , Mycobacterium Infections, Nontuberculous , Mycobacterium abscessus , beta-Lactamase Inhibitors , beta-Lactams , Humans , Mycobacterium abscessus/drug effects , Mycobacterium abscessus/isolation & purification , beta-Lactamase Inhibitors/pharmacology , Mycobacterium Infections, Nontuberculous/microbiology , Mycobacterium Infections, Nontuberculous/drug therapy , Anti-Bacterial Agents/pharmacology , beta-Lactams/pharmacology , Boronic Acids/pharmacology
8.
Plant Physiol Biochem ; 213: 108823, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38905727

ABSTRACT

Cadmium (Cd) is a widely distributed heavy metal pollutant that is detrimental to growth and development of plants. The secretion of indole-3-acetic acid is one of the defense mechanisms when plants inflict heavy metal stress. This study aimed to explore how 4-phenoxyphenylboronic acid, an effective IAA inhibitor, induces changes in IAA level, Cadmium accumulation, and activation of defense responses in rice seedling roots under different Cadmium concentrations. Our research results show that: 1) root growth was promoted with PPBa addition under mild Cadmium treatment. 2) the root IAA level improved with increasing Cadmium concentration, and PPBa had a significant inhibitory effect on IAA level. 3) PPBa had no effect on the Cadmium accumulation in rice seedling roots. 4) PPBa had a significant inhibitory effect on the generation of H2O2 under mild and moderate Cadmium treatment. 5) PPBa exacerbated the imbalance of osmotic substances in rice seedling roots under severe Cadmium treatment. This study helps us understand the tolerance and endogenous regulation of plants to heavy metal stress.


Subject(s)
Cadmium , Hydrogen Peroxide , Indoleacetic Acids , Oryza , Plant Roots , Seedlings , Oryza/drug effects , Oryza/metabolism , Oryza/growth & development , Indoleacetic Acids/metabolism , Cadmium/toxicity , Cadmium/metabolism , Plant Roots/drug effects , Plant Roots/metabolism , Plant Roots/growth & development , Seedlings/drug effects , Seedlings/metabolism , Seedlings/growth & development , Hydrogen Peroxide/metabolism , Stress, Physiological/drug effects , Boronic Acids/pharmacology
9.
Biomacromolecules ; 25(7): 4215-4232, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38845149

ABSTRACT

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


Subject(s)
Boron Neutron Capture Therapy , Micelles , Boron Neutron Capture Therapy/methods , Animals , Mice , Melanoma, Experimental/pathology , Melanoma, Experimental/drug therapy , Boronic Acids/chemistry , Cell Line, Tumor , Polyethylene Glycols/chemistry , Polymers/chemistry , Mice, Inbred C57BL , Esters/chemistry , Esters/pharmacology , Boron Compounds/chemistry , Boron Compounds/pharmacology
10.
Int J Biol Macromol ; 273(Pt 1): 132737, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38825265

ABSTRACT

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


Subject(s)
Antineoplastic Agents , Berberine , Boronic Acids , Glucans , Nanoparticles , Skin Neoplasms , Spheroids, Cellular , Humans , Berberine/chemistry , Berberine/pharmacology , Glucans/chemistry , Glucans/pharmacology , Boronic Acids/chemistry , Nanoparticles/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Cell Line, Tumor , Spheroids, Cellular/drug effects , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Particle Size , Drug Carriers/chemistry , Drug Liberation , Cell Survival/drug effects
11.
Int J Biol Macromol ; 273(Pt 1): 133062, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38862051

ABSTRACT

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


Subject(s)
Anti-Bacterial Agents , Boronic Acids , Curcumin , Dextrans , Diabetes Mellitus, Experimental , Wound Healing , Curcumin/pharmacology , Curcumin/chemistry , Animals , Wound Healing/drug effects , Dextrans/chemistry , Mice , Boronic Acids/chemistry , Boronic Acids/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Diabetes Mellitus, Experimental/drug therapy , Nanoparticles/chemistry , Drug Liberation , Drug Carriers/chemistry , RAW 264.7 Cells , Male , Antioxidants/pharmacology , Antioxidants/chemistry , Bacterial Infections/drug therapy
12.
Molecules ; 29(11)2024 May 25.
Article in English | MEDLINE | ID: mdl-38893376

ABSTRACT

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


Subject(s)
Ellagic Acid , Molecular Imprinting , Solid Phase Extraction , Ellagic Acid/chemistry , Solid Phase Extraction/methods , Molecular Imprinting/methods , Boronic Acids/chemistry , Molecularly Imprinted Polymers/chemistry , Food Analysis/methods , Nanostructures/chemistry
13.
Nat Commun ; 15(1): 5228, 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38898022

ABSTRACT

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


Subject(s)
Boronic Acids , Palladium , Palladium/chemistry , Catalysis , Boronic Acids/chemistry , Glycosides/chemistry , Glycosides/chemical synthesis , DNA/chemistry
14.
Spectrochim Acta A Mol Biomol Spectrosc ; 319: 124550, 2024 Oct 15.
Article in English | MEDLINE | ID: mdl-38823240

ABSTRACT

Near-infrared organic fluorescent probes have great need in biological sciences and medicine but most of them are still largely unable to meet demand. In this work, a delicate multipurpose organic fluorescent probe (DPPM-TPA) with aggregation-induced emission performances is designed and prepared by facile method to reflect fluorescence labeling, two-photon imaging, and long-term fluorescent tracking. Specifically, DPPM-TPA NPs was constructed from 4-(diphenylamino)phenylboronic acid and DPPM-Br by classical Suzuki coupling reaction and then coated with F127. Such nanoprobe possessed high stability in diverse medium under ambient temperatures, low cytotoxicity, and brilliant fluorescence performance. More importantly, DPPM-TPA NPs showed excellent two-photon imaging and extraordinary long-term fluorescence tracing capacity to malignant tumor, and it can last up to 9 days. These results indicated that DPPM-TPA NPs is expected to serve as a fluorescent probe for photodiagnostic and providing a new idea for the development of long-term fluorescent tracker.


Subject(s)
Fluorescent Dyes , Fluorescent Dyes/chemistry , Humans , Animals , Neoplasms , Mice , Spectrometry, Fluorescence , Nanoparticles/chemistry , Cell Line, Tumor , Boronic Acids/chemistry
15.
Carbohydr Polym ; 339: 122262, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-38823926

ABSTRACT

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


Subject(s)
Anti-Bacterial Agents , Chitosan , Hydrogels , Neoplasm Recurrence, Local , Polyvinyl Alcohol , Tannins , Chitosan/chemistry , Chitosan/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Hydrogen-Ion Concentration , Animals , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Polyvinyl Alcohol/chemistry , Mice , Neoplasm Recurrence, Local/prevention & control , Tannins/chemistry , Tannins/pharmacology , Humans , Staphylococcus aureus/drug effects , Boronic Acids/chemistry , Escherichia coli/drug effects , Cell Line, Tumor , Reactive Oxygen Species/metabolism , Iron/chemistry , Surgical Wound Infection/prevention & control
16.
Asian Pac J Cancer Prev ; 25(6): 1959-1967, 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38918657

ABSTRACT

BACKGROUND: As one of the main molecules in BCR-ABL signaling, c-Myc acts as a pivotal key in disease progression and disruption of long-term remission in patients with CML. OBJECTIVES: To clarify the effects of c-Myc inhibition in CML, we examined the anti-tumor property of a well-known small molecule inhibitor of c-Myc 10058-F4 on K562 cell line. METHODS: This experimental study was conducted in K562 cell line for evaluation of cytotoxic activity of 10058-F4 using Trypan blue and MTT assays. Flow cytometry and Quantitative RT-PCR analysis were also conducted to determine its mechanism of action. Additionally, Annexin/PI staining was performed for apoptosis assessment. RESULTS: The results of Trypan blue and MTT assay demonstrated that inhibition of c-Myc, as shown by suppression of c-Myc expression and its associated genes PP2A, CIP2A, and hTERT, could decrease viability and metabolic activity of K562 cells, respectively. Moreover, a robust elevation in cell population in G1-phase coupled with up-regulation of p21 and p27 expression shows that 10058-F4 could hamper cell proliferation, at least partly, through induction of G1 arrest. Accordingly, we found that 10058-F4 induced apoptosis via increasing Bax and Bad; In contrast, no significant alterations were observed NF-KB pathway-targeted anti-apoptotic genes in the mRNA levels. Notably, disruption of the NF-κB pathway with bortezomib as a common proteasome inhibitor sensitized K562 cells to the cytotoxic effect of 10058-F4, substantiating the fact that the NF-κB axis functions probably attenuate the K562 cells sensitivity to c-Myc inhibition. CONCLUSIONS: It can be concluded from the results of this study that inhibition of c-Myc induces anti-neoplastic effects on CML-derived K562 cells as well as increases the efficacy of imatinib. For further insight into the safety and effectiveness of 10058-F4 in CML, in vivo studies will be required.


Subject(s)
Apoptosis , Cell Proliferation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Proto-Oncogene Proteins c-myc , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Proto-Oncogene Proteins c-myc/metabolism , Proto-Oncogene Proteins c-myc/genetics , Apoptosis/drug effects , Cell Proliferation/drug effects , K562 Cells , NF-kappa B/metabolism , NF-kappa B/antagonists & inhibitors , Antineoplastic Agents/pharmacology , Bortezomib/pharmacology , Tumor Cells, Cultured , Boronic Acids/pharmacology , RNA, Messenger/genetics , Pyrazines/pharmacology , Signal Transduction/drug effects , Telomerase/antagonists & inhibitors
17.
ACS Nano ; 18(26): 16752-16765, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38901038

ABSTRACT

Although lateral flow immunochromatographic assay (LFIA) is an effective point-of-care testing technology, it still cannot achieve broad-spectrum and ultrasensitive detection of viruses. Herein, we propose a multiplex LFIA platform using a two-dimensional graphene oxide (GO)-based magnetic fluorescent nanofilm (GF@DQD) as a multifunctional probe and 4-aminophenylboronic acid (APBA) as a broad-spectrum recognition molecule for viral glycoprotein detection. GF@DQD-APBA with enhanced magnetic/fluorescence properties and universal capture ability for multiple viruses was easily prepared through the electrostatic adsorption of one layer of density-controlled Fe3O4 nanoparticles (NPs) and thousands of small CdSe/ZnS-MPA quantum dots (QDs) on a monolayer GO sheet followed by chemical coupling with APBA on the QD surface. The GF@DQD-APBA probe enabled the universal capture and specific determination of different target viruses on the test strip through an arbitrary combination with the antibody-modified LFIA strip, thus greatly improving detection efficiency and reducing the cost and difficulty of multiplex LFIA for viruses. The proposed technique can simultaneously and sensitively diagnose three newly emerged viruses within 20 min with detection limits down to the pg/mL level. The excellent practicability of GF@DQD-APBA-LFIA was also demonstrated in the detection of 34 clinical specimens positive for SARS-CoV-2, revealing its potential for epidemic control and on-site viral detection.


Subject(s)
Boronic Acids , Graphite , Quantum Dots , Quantum Dots/chemistry , Boronic Acids/chemistry , Immunoassay/methods , Humans , Graphite/chemistry , Limit of Detection , SARS-CoV-2/isolation & purification , SARS-CoV-2/immunology , Magnetite Nanoparticles/chemistry , COVID-19/diagnosis , COVID-19/virology
19.
Colloids Surf B Biointerfaces ; 239: 113939, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38744077

ABSTRACT

Chronic infections caused by the pathogenic biofilms on implantable medical devices pose an increasing challenge. To combat long-term biofilm-associated infections, we developed a novel dual-functional polymer coating with antibacterial and antifouling properties. The coating consists of N-vinylpyrrolidone (NVP) and 3-(acrylamido)phenylboronic acid (APBA) copolymer brushes, which bind to curcumin (Cur) as antibacterial molecules through acid-responsive boronate ester bonds. In this surface design, the hydrophilic poly (N-vinylpyrrolidone) (PVP) component improved antifouling performance and effectively prevented bacterial adhesion and aggregation during the initial phases. The poly (3-(acrylamido) phenylboronic acid) (PAPBA, abbreviated PB) component provided binding sites for Cur by forming acid-responsive boronate ester bonds. When fewer bacteria overcame the anti-adhesion barrier and colonized, the surface responded to the decreased microenvironmental pH by breaking the boronate ester bonds and releasing curcumin. This responsive mechanism enabled Cur to interfere with biofilm formation and provide a multilayer anti-biofilm protection system. The coating showed excellent antibacterial properties against Escherichia coli and Staphylococcus aureus, preventing biofilm formation for up to 7 days. The coating also inhibited protein adsorption and platelet adhesion significantly. This coating also exhibited high biocompatibility with animal erythrocytes and pre-osteoblasts. This research offers a promising approach for developing novel smart anti-biofilm coating materials.


Subject(s)
Anti-Bacterial Agents , Biofilms , Curcumin , Escherichia coli , Polymers , Staphylococcus aureus , Biofilms/drug effects , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Escherichia coli/drug effects , Staphylococcus aureus/drug effects , Polymers/chemistry , Polymers/pharmacology , Curcumin/pharmacology , Curcumin/chemistry , Bacterial Adhesion/drug effects , Coated Materials, Biocompatible/chemistry , Coated Materials, Biocompatible/pharmacology , Animals , Microbial Sensitivity Tests , Boronic Acids/chemistry , Boronic Acids/pharmacology , Surface Properties , Humans , Biofouling/prevention & control , Hydrogen-Ion Concentration
20.
Analyst ; 149(12): 3363-3371, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38712505

ABSTRACT

Specific detection of glycoproteins such as transferrin (TRF) related to neurological diseases, hepatoma and other diseases always plays an important role in the field of disease diagnosis. We designed an antibody-free immunoassay sensing method based on molecularly imprinted polymers (MIPs) formed by the polymerization of multiple functional monomers for the sensitive and selective detection of TRF in human serum. In the sandwich surface-enhanced Raman spectroscopy (SERS) sensor, the TRF-oriented magnetic MIP nanoparticles (Fe3O4@SiO2-MIPs) served as capture units to specifically recognize TRF and 4-mercaptophenylboronic acid-functionalized gold nanorods (MPBA-Au NRs) served as SERS probes to label the targets. In order to achieve stronger interaction between the recognition cavities of the prepared MIPs and the different amino acid fragments that make up TRF, Fe3O4@SiO2-MIPs were obtained through polycondensation reactions between more silylating reagents, enhancing the specific recognition of the entire TRF protein and achieving high IF. This sensing method exhibited a good linear response to TRF within the TRF concentration range of 0.01 ng mL-1 to 1 mg mL-1 (R2 = 0.9974), and the LOD was 0.00407 ng mL-1 (S/N = 3). The good stability, reproducibility and specificity of the resulting MIP based SERS sensor were demonstrated. The determination of TRF in human serum confirmed the feasibility of the method in practical applications.


Subject(s)
Gold , Molecularly Imprinted Polymers , Silicon Dioxide , Spectrum Analysis, Raman , Transferrin , Humans , Spectrum Analysis, Raman/methods , Transferrin/analysis , Transferrin/chemistry , Gold/chemistry , Molecularly Imprinted Polymers/chemistry , Silicon Dioxide/chemistry , Limit of Detection , Nanotubes/chemistry , Magnetite Nanoparticles/chemistry , Molecular Imprinting/methods , Boronic Acids/chemistry , Polymers/chemistry , Sulfhydryl Compounds
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