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1.
Sci Adv ; 10(28): eado1453, 2024 Jul 12.
Article de Anglais | MEDLINE | ID: mdl-38985862

RÉSUMÉ

The interplay between humans and their microbiome is crucial for various physiological processes, including nutrient absorption, immune defense, and maintaining homeostasis. Microbiome alterations can directly contribute to diseases or heighten their likelihood. This relationship extends beyond humans; microbiota play vital roles in other organisms, including eukaryotic pathogens causing severe diseases. Notably, Wolbachia, a bacterial microbiota, is essential for parasitic worms responsible for lymphatic filariasis and onchocerciasis, devastating human illnesses. Given the lack of rapid cures for these infections and the limitations of current treatments, new drugs are imperative. Here, we disrupt Wolbachia's symbiosis with pathogens using boron-based compounds targeting an unprecedented Wolbachia enzyme, leucyl-tRNA synthetase (LeuRS), effectively inhibiting its growth. Through a compound demonstrating anti-Wolbachia efficacy in infected cells, we use biophysical experiments and x-ray crystallography to elucidate the mechanism behind Wolbachia LeuRS inhibition. We reveal that these compounds form adenosine-based adducts inhibiting protein synthesis. Overall, our study underscores the potential of disrupting key microbiota to control infections.


Sujet(s)
Microbiote , Wolbachia , Wolbachia/effets des médicaments et des substances chimiques , Humains , Animaux , Leucine-tRNA ligase/métabolisme , Leucine-tRNA ligase/antagonistes et inhibiteurs , Amino acyl-tRNA synthetases/métabolisme , Amino acyl-tRNA synthetases/antagonistes et inhibiteurs , Cristallographie aux rayons X , Composés du bore/pharmacologie , Composés du bore/composition chimique , Symbiose , Modèles moléculaires
2.
J Cancer Res Clin Oncol ; 150(7): 334, 2024 Jul 05.
Article de Anglais | MEDLINE | ID: mdl-38969842

RÉSUMÉ

PURPOSE: Proteasome inhibitors (PIs), which cause cell death via tumor suppressor and pro-apoptotic proteins, are integral to treatment of many hematologic malignancies but are limited by their gastrointestinal adverse effects. Evidence regarding these PI-related adverse effects is scant. In this study, we evaluated gastrointestinal adverse events caused by PIs and compared gastrointestinal toxicities between bortezomib, carfilzomib, and ixazomib. METHODS: We conducted a retrospective study of cancer patients treated with PIs at a tertiary care cancer center to investigate the clinical characteristics of PI-related gastrointestinal adverse events. RESULTS: Our sample comprised 973 patients with PI exposure and stool studies ordered between January 2017 and December 2022. Of these, 193 patients (20%) had PI-related gastrointestinal toxicity based on clinical symptoms and stool study results. The most common symptom was diarrhea, present in 169 (88% of those with gastrointestinal toxicity). Twenty-two (11%) required hospitalization, and 71 (37%) developed recurrence of symptoms. Compared to bortezomib or carfilzomib, ixazomib had a longer interval from PI initiation to the onset of gastrointestinal symptoms (313 days vs 58 days vs 89 days, p = 0.002) and a significantly lower percentage of diarrhea-predominant presentation of gastrointestinal toxicity (71% vs 96% vs 91%, p = 0.048). CONCLUSION: While PI-related gastrointestinal toxicities have various presentations and courses based on different regimens, the vast majority of patients presented with milder disease behavior. Despite a considerably high rate of hospitalization and recurrence after treatment necessitating optimization of clinical management, our cohort demonstrates favorable outcomes without long-term consequences.


Sujet(s)
Composés du bore , Bortézomib , Maladies gastro-intestinales , Glycine , Inhibiteurs du protéasome , Humains , Inhibiteurs du protéasome/effets indésirables , Mâle , Femelle , Études rétrospectives , Adulte d'âge moyen , Composés du bore/effets indésirables , Composés du bore/usage thérapeutique , Sujet âgé , Glycine/analogues et dérivés , Glycine/effets indésirables , Bortézomib/effets indésirables , Bortézomib/administration et posologie , Maladies gastro-intestinales/induit chimiquement , Oligopeptides/effets indésirables , Adulte , Sujet âgé de 80 ans ou plus
3.
ACS Appl Mater Interfaces ; 16(24): 30622-30635, 2024 Jun 19.
Article de Anglais | MEDLINE | ID: mdl-38857197

RÉSUMÉ

Mo4/3B2-x nanosheets are newly developed, and 2D transition metal borides (MBene) were reported in 2021, but there is no report on their further applications and modification; hence, this article sheds light on the significance of potential biological prospects for future biomedical applications. Therefore, elucidation of the biocompatibility, biotoxicology, and bioactivity of Mo4/3B2-x nanosheets has been an urgent need to be fulfilled. Nanometabolomics (also referred as nanomaterials-based metabolomics) was first proposed and utilized in our previous work, which specialized in interpreting nanomaterials-induced metabolic reprogramming through aqueous metabolomics and lipidomics approach. Hence, nanometabolomics could be considered as a novel concept combining nanoscience and metabolomics to provide bioinformation on nanomaterials' biomedical applications. In this work, the safe range of concentration (<50 mg/L) with good biosafety toward human umbilical vein endothelial cells (HUVECs) was discovered. The low concentration (5 mg/L) and high concentration (50 mg/L) of Mo4/3B2-x nanosheets were utilized for the in vitro Mo4/3B2-x-cell interaction. Nanometabolomics has elucidated the biological prospective of Mo4/3B2-x nanosheets via monitoring its biocompatibility and metabolic shift of HUVECs. The results revealed that 50 mg/L Mo4/3B2-x nanosheets could lead to a stronger alteration of amino acid metabolism with disturbance of the corresponding amino acid-related pathways (including amino acid metabolism, amino acid degradation, fatty acid biosynthesis, and lipid biosynthesis and metabolism). These interesting results were closely involved with the oxidative stress and production of excess ROS. This work could be regarded as a pathbreaking study on Mo4/3B2-x nanosheets at a biological level, which also designates their further biochemical, medical, and industrial application and development based on nanometabolomics bioinformation.


Sujet(s)
Acides aminés , Cellules endothéliales de la veine ombilicale humaine , Nanostructures , Humains , Cellules endothéliales de la veine ombilicale humaine/métabolisme , Acides aminés/composition chimique , Acides aminés/métabolisme , Nanostructures/composition chimique , Nanostructures/toxicité , Métabolomique , Matériaux biocompatibles/composition chimique , Matériaux biocompatibles/pharmacologie , Composés du bore/composition chimique , Composés du bore/pharmacologie , Espèces réactives de l'oxygène/métabolisme ,
4.
Sci Rep ; 14(1): 13950, 2024 06 17.
Article de Anglais | MEDLINE | ID: mdl-38886395

RÉSUMÉ

Tumor-to-normal ratio (T/N) measurement of 18F-FBPA is crucial for patient eligibility to receive boron neutron capture therapy. This study aims to compare the difference in standard uptake value ratios on brain tumors and normal brains using PET/MR ZTE and atlas-based attenuation correction with the current standard PET/CT attenuation correction. Regarding the normal brain uptake, the difference was not significant between PET/CT and PET/MR attenuation correction methods. The T/N ratio of PET/CT-AC, PET/MR ZTE-AC and PET/MR AB-AC were 2.34 ± 0.95, 2.29 ± 0.88, and 2.19 ± 0.80, respectively. The T/N ratio comparison showed no significance using PET/CT-AC and PET/MR ZTE-AC. As for the PET/MRI AB-AC, significantly lower T/N ratio was observed (- 5.18 ± 9.52%; p < 0.05). The T/N difference between ZTE-AC and AB-AC was also significant (4.71 ± 5.80%; p < 0.01). Our findings suggested PET/MRI imaging using ZTE-AC provided superior quantification on 18F-FBPA-PET compared to atlas-based AC. Using ZTE-AC on 18F-FBPA-PET /MRI might be crucial for BNCT pre-treatment planning.


Sujet(s)
Thérapie par capture de neutrons par le bore , Tumeurs du cerveau , Imagerie par résonance magnétique , Tomographie par émission de positons couplée à la tomodensitométrie , Humains , Thérapie par capture de neutrons par le bore/méthodes , Tumeurs du cerveau/radiothérapie , Tumeurs du cerveau/imagerie diagnostique , Femelle , Mâle , Imagerie par résonance magnétique/méthodes , Tomographie par émission de positons couplée à la tomodensitométrie/méthodes , Adulte d'âge moyen , Tomographie par émission de positons/méthodes , Adulte , Sujet âgé , Encéphale/imagerie diagnostique , Radio-isotopes du fluor , Composés du bore , Phénylalanine/analogues et dérivés
5.
PLoS One ; 19(6): e0302157, 2024.
Article de Anglais | MEDLINE | ID: mdl-38889107

RÉSUMÉ

Borophene nanosheets appear in various sizes and shapes, ranging from simple planar structures to complicated polyhedral formations. Due to their unique chemical, optical, and electrical properties, Borophene nanosheets are theoretically and practically attractive and because of their high thermal conductivity, boron nanosheets are suitable for efficient heat transmission applications. In this paper, temperature indices of borophene nanosheets are computed and these indices are employed in QSPR analysis of attributes like Young's modulus, Shear modulus, and Poisson's ratio of borophene nanosheets and borophene ß12 sheets. The regression model for the F-Temperature index is discovered to be the best fit for shear modulus, the reciprocal product connectivity temperature index is discovered to be fit for Poisson's ratio and the second hyper temperature index is discovered to be fit for Young's modulus based on the correlation coefficient.


Sujet(s)
Composés du bore , Module d'élasticité , Nanostructures , Nanostructures/composition chimique , Composés du bore/composition chimique , Température , Relation quantitative structure-activité , Conductivité thermique
6.
Chemosphere ; 361: 142493, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38823426

RÉSUMÉ

Lignin-based carbon material can be utilized as carbonaceous adsorbents for the removal of toxic gaseous organic pollutants, while the poor heat-resistance limited its widely application. Here in, B-N co-doped lignin carbon (BN-C) with high thermal stability was synthesized, and the optimized BN-C (1:2) exhibited notably improved heat resistance with the decomposition temperature up to 505 °C, and excellent adsorption capacity for o-dichlorobenzene (o-DCB) (1510.0 mg/g) and toluene (947.3 mg/g), together with good cyclic stability over 10 cycles for o-dichlorobenzene. The existence of abundant hexagonal boron nitride (h-BN) with good thermal conductivity contributed to the superior heat-resistance of BN-C (1:2), and the high specific surface area (1764.5 m2/g), enriched hydroxyl functional groups and improved graphitization degree contributed to its enhanced adsorption performance. More importantly, BN-C (1:2) supported Ru could effectively remove o-DCB and toluene at wide temperature range (50-300 °C). The present work guided the development of heat-resistant lignin-derived adsorbent-catalyst for gaseous aromatic pollutants removal, which benefits both environmental protection and resource utilization.


Sujet(s)
Polluants atmosphériques , Lignine , Azote , Adsorption , Lignine/composition chimique , Catalyse , Azote/composition chimique , Polluants atmosphériques/composition chimique , Température élevée , Bore/composition chimique , Toluène/composition chimique , Composés du bore/composition chimique , Carbone/composition chimique
7.
Comput Biol Chem ; 111: 108112, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38843583

RÉSUMÉ

Venous leg ulcers (VLUs) pose a growing healthcare challenge due to aging, obesity, and sedentary lifestyles. Despite various treatments available, addressing the complex nature of VLUs remains difficult. In this context, this study investigates repurposing boronated drugs to inhibit arginase 1 activity for VLU treatment. The molecular docking study conducted by Schrodinger GLIDE targeted the binuclear manganese cluster of arginase 1 enzyme (2PHO). Further, the ligand-protein complex was subjected to molecular dynamic studies at 500 ns in Gromacs-2019.4. Trajectory analysis was performed using the GROMACS simulation package of protein RMSD, RMSF, RG, SASA, and H-Bond. The docking study revealed intriguing results where the tavaborole showed a better docking score (-3.957 Kcal/mol) compared to the substrate L-arginine (-3.379 Kcal/mol) and standard L-norvaline (-3.141 Kcal/mol). Tavaborole interaction with aspartic acid ultimately suggests that the drug molecule binds to the catalytic site of arginase 1, potentially influencing the enzyme's function. The dynamics study revealed the compounds' stability and compactness of the protein throughout the simulation. The RMSD, RMSF, SASA, RG, inter and intra H-bond, PCA, FEL, and MMBSA studies affirmed the ligand-protein and protein complex flexibility, compactness, binding energy, van der waals energy, and solvation dynamics. These results revealed the stability and the interaction of the ligand with the catalytic site of arginase 1 enzyme, triggering the study towards the VLU treatment.


Sujet(s)
Arginase , Simulation de docking moléculaire , Arginase/antagonistes et inhibiteurs , Arginase/métabolisme , Arginase/composition chimique , Humains , Ulcère variqueux/traitement médicamenteux , Composés du bore/composition chimique , Composés du bore/pharmacologie , Repositionnement des médicaments , Simulation de dynamique moléculaire , Antienzymes/composition chimique , Antienzymes/pharmacologie , Composés hétérocycliques bicycliques/composition chimique , Composés hétérocycliques bicycliques/métabolisme , Structure moléculaire
8.
Int J Mol Sci ; 25(12)2024 Jun 11.
Article de Anglais | MEDLINE | ID: mdl-38928126

RÉSUMÉ

Photodynamic Therapy (PDT) is recognized for its exceptional effectiveness as a promising cancer treatment method. However, it is noted that overexposure to the dosage and sunlight in traditional PDT can result in damage to healthy tissues, due to the low tumor selectivity of currently available photosensitizers (PSs). To address this challenge, we introduce herein a new strategy where the small molecule-targeted agent, erlotinib, is integrated into a boron dipyrromethene (BODIPY)-based PS to form conjugate 6 to enhance the precision of PDT. This conjugate demonstrates optical absorption, fluorescence emission, and singlet oxygen generation efficiency comparable to the reference compound 7, which lacks erlotinib. In vitro studies reveal that, after internalization, conjugate 6 predominantly accumulates in the lysosomes of HepG2 cells, exhibiting significant photocytotoxicity with an IC50 value of 3.01 µM. A distinct preference for HepG2 cells over HELF cells is observed with conjugate 6 but not with compound 7. In vivo experiments further confirm that conjugate 6 has a specific affinity for tumor tissues, and the combination treatment of conjugate 6 with laser illumination can effectively eradicate H22 tumors in mice with outstanding biosafety. This study presents a novel and potential PS for achieving precise PDT against cancer.


Sujet(s)
Chlorhydrate d'erlotinib , Tumeurs du foie , Photothérapie dynamique , Photosensibilisants , Porphobilinogène , Humains , Photothérapie dynamique/méthodes , Animaux , Souris , Porphobilinogène/analogues et dérivés , Porphobilinogène/composition chimique , Photosensibilisants/pharmacologie , Photosensibilisants/composition chimique , Cellules HepG2 , Tumeurs du foie/traitement médicamenteux , Tumeurs du foie/anatomopathologie , Chlorhydrate d'erlotinib/pharmacologie , Chlorhydrate d'erlotinib/composition chimique , Composés du bore/composition chimique , Composés du bore/pharmacologie
9.
J Control Release ; 371: 445-454, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38844180

RÉSUMÉ

In boron neutron capture therapy (BNCT), boron drugs should exhibit high intratumoral boron concentrations during neutron irradiation, while being cleared from the blood and normal organs. However, it is usually challenging to achieve such tumor accumulation and quick clearance simultaneously in a temporally controlled manner. Here, we developed a polymer-drug conjugate that can actively control the clearance of the drugs from the blood. This polymer-drug conjugate is based on a biocompatible polymer that passively accumulates in tumors. Its side chains were conjugated with the low-molecular-weight boron drugs, which are immediately excreted by the kidneys, via photolabile linkers. In a murine subcutaneous tumor model, the polymer-drug conjugate could accumulate in the tumor with the high boron concentration ratio of the tumor to the surrounding normal tissue (∼10) after intravenous injection while a considerable amount remained in the bloodstream as well. Photoirradiation to blood vessels through the skin surface cleaved the linker to release the boron drug in the blood, allowing for its rapid clearance from the bloodstream. Meanwhile, the boron concentration in the tumor which was not photoirradiated could be maintained high, permitting strong BNCT effects. In clinical BNCT, the dose of thermal neutrons to solid tumors is determined by the maximum radiation exposure to normal organs. Thus, our polymer-drug conjugate may enable us to increase the therapeutic radiation dose to tumors in such a practical situation.


Sujet(s)
Thérapie par capture de neutrons par le bore , Polymères , Thérapie par capture de neutrons par le bore/méthodes , Animaux , Polymères/composition chimique , Polymères/pharmacocinétique , Polymères/administration et posologie , Lignée cellulaire tumorale , Composés du bore/pharmacocinétique , Composés du bore/administration et posologie , Composés du bore/composition chimique , Lumière , Femelle , Souris , Tumeurs/radiothérapie , Tumeurs/traitement médicamenteux , Bore/pharmacocinétique , Bore/administration et posologie , Bore/composition chimique , Souris de lignée BALB C , Humains
10.
Anal Chim Acta ; 1313: 342700, 2024 Jul 18.
Article de Anglais | MEDLINE | ID: mdl-38862203

RÉSUMÉ

BACKGROUND: L-p-Boronophehylalanine (BPA) is used in boron neutron capture therapy (BNCT), which is a novel selective cancer radiotherapy technique. It is important to measure BPA levels in human blood for effective radiotherapy; a prompt gamma-ray spectrometer, ICP-AES, and ICP-MS have been used for this purpose. However, these methods require sophisticated and expensive apparatuses as well as experienced analysts. Herein, we propose an HPLC-FL method for the determination of BPA after precolumn derivatization. A new fluorogenic reagent for aryl boronic acid derivatives, namely, 4-iodobenzonitrile, was employed for the fluorogenic derivatization of BPA based on the Suzuki coupling reaction. RESULTS: After the fluorogenic derivatization, a fluorescent cyanobiphenyl derivative is formed with maximum fluorescence at 335 nm after excitation at 290 nm. The developed method showed good linearity (r2=0.997) over the concentration range of 0.5-1000 nmol/L, and the detection limit (S/N = 3) was 0.26 nmol/L. The proposed method is more sensitive than previously reported methods for the determination of BPA, including the ICP-MS. Finally, the proposed method was successively applied to the measurement of BPA in human whole blood samples with a good recovery rate (≥95.7 %) using only 10 µL of blood sample. The proposed method offers a simple and efficient solution for monitoring BPA levels in BNCT-treated patients. SIGNIFICANCE: 4-Iodobenzonitrile was investigated as a new fluorogenic reagent for BPA based on Suzuki coupling. A new HPLC-FL method for BPA in whole blood samples with ultrasensitivity was developed. The developed method is superior in sensitivity to all previously reported methods for BPA. The method requires only a very small sample volume, making it suitable for micro-blood analysis of BPA via fingerstick sampling.


Sujet(s)
Colorants fluorescents , Nitriles , Phénylalanine , Humains , Nitriles/composition chimique , Nitriles/sang , Chromatographie en phase liquide à haute performance/méthodes , Colorants fluorescents/composition chimique , Phénylalanine/sang , Phénylalanine/analogues et dérivés , Phénylalanine/composition chimique , Spectrométrie de fluorescence/méthodes , Limite de détection , Composés du bore/composition chimique , Composés du bore/sang
11.
Theranostics ; 14(8): 3193-3212, 2024.
Article de Anglais | MEDLINE | ID: mdl-38855185

RÉSUMÉ

As a developing radiation treatment for tumors, neutron capture therapy (NCT) has less side effects and a higher efficacy than conventional radiation therapy. Drugs with specific isotopes are indispensable counterparts of NCT, as they are the indespensable part of the neutron capture reaction. Since the creation of the first and second generations of boron-containing reagents, NCT has significantly advanced. Notwithstanding, the extant NCT medications, predominantly comprised of small molecule boron medicines, have encountered challenges such monofunctionality, inadequate targeting of tumors, and hypermetabolism. There is an urgent need to promote the research and development of new types of NCT drugs. Bio-nanomaterials can be introduced into the realm of NCT, and nanotechnology can give conventional medications richer functionality and significant adaptability. This can complement the advantages of each other and is expected to develop more new drugs with less toxicity, low side effects, better tumor targeting, and high biocompatibility. In this review, we summarized the research progress of nano-drugs in NCT based on the different types and sources of isotopes used, and introduced the attempts and efforts made by relevant researchers in combining nanomaterials with NCT, hoping to provide pivotal references for promoting the development of the field of tumor radiotherapy.


Sujet(s)
Tumeurs , Humains , Tumeurs/radiothérapie , Tumeurs/traitement médicamenteux , Animaux , Thérapie par capture de neutrons/méthodes , Nanoparticules/composition chimique , Nanostructures/usage thérapeutique , Nanostructures/composition chimique , Nanotechnologie/méthodes , Thérapie par capture de neutrons par le bore/méthodes , Composés du bore/usage thérapeutique , Composés du bore/composition chimique , Composés du bore/pharmacologie
12.
J Mater Chem B ; 12(25): 6175-6189, 2024 Jun 27.
Article de Anglais | MEDLINE | ID: mdl-38831689

RÉSUMÉ

In this study, the heavy-atom-free BODIPY dendrimer TM4-BDP was synthesized for near-infrared photodynamic therapy, and was composed of a triphenylamine-BODIPY dimer and four 1-(2-morpholinoethyl)-1H-indole-3-ethenyl groups. The TM4-BDP could achieve near-infrared photodynamic therapy through two different photosensitive pathways, which include one-photon excitation at 660 nm and two-photon excitation at 1000 nm. In the one-photon excitation pathway, the TM4-BDP could generate singlet oxygen and superoxide radicals under 660 nm illumination. In addition, the one-photon PDT experiment in human nasopharyngeal carcinoma (CNE-2) cells also indicated that the TM4-BDP could specifically accumulate in lysosomes and show great cell phototoxicity with an IC50 of 22.1 µM. In the two-photon excitation pathway, the two-photon absorption cross-section at 1030 nm of TM4-BDP was determined to be 383 GM, which means that it could generate reactive oxygen species (ROS) under 1000 nm femtosecond laser excitation. Moreover, the two-photon PDT experiment in zebrafish also indicated the TM4-BDP could be used for two-photon fluorescence imaging and two-photon induced ROS generation in biological environments. Furthermore, in terms of the ROS generation mechanism, the TM4-BDP employed a novel spin-vibronic coupling intersystem crossing (SV-ISC) process for the mechanism of ROS generation and the femtosecond transient absorption spectra indicated that this novel SV-ISC mechanism was closely related to its charge transfer state lifetime. These above experiments of TM4-BDP demonstrate that the dendrimer design is an effective strategy for constructing heavy-atom-free BODIPY photosensitizers in the near-infrared region and lay the foundation for two-photon photodynamic therapy in future clinical trials.


Sujet(s)
Composés du bore , Dendrimères , Photothérapie dynamique , Photons , Photosensibilisants , Danio zébré , Animaux , Composés du bore/composition chimique , Composés du bore/pharmacologie , Composés du bore/synthèse chimique , Dendrimères/composition chimique , Dendrimères/pharmacologie , Dendrimères/synthèse chimique , Photosensibilisants/composition chimique , Photosensibilisants/pharmacologie , Photosensibilisants/synthèse chimique , Humains , Structure moléculaire , Espèces réactives de l'oxygène/métabolisme , Survie cellulaire/effets des médicaments et des substances chimiques , Lignée cellulaire tumorale
13.
J Mater Chem B ; 12(25): 6128-6136, 2024 Jun 27.
Article de Anglais | MEDLINE | ID: mdl-38836578

RÉSUMÉ

Boron neutron capture therapy (BNCT) is an emerging approach for treating malignant tumors with binary targeting. However, its clinical application has been hampered by insufficient 10B accumulation in tumors and low 10B concentration ratios of tumor-to-blood (T/B) and tumor-to-normal tissue (T/N). Herein, we developed fluorinated BPA derivatives with different fluorine groups as boron delivery agents for enabling sufficient 10B accumulation in tumors and enhancing T/B and T/N ratios. Our findings demonstrated that fluorinated BPA derivatives had good biological safety. Furthermore, fluorinated BPA derivatives showed improved 10B accumulation in tumors and enhanced T/B and T/N ratios compared to the clinical boron drug fructose-BPA (f-BPA). In particular, in B16-F10 tumor-bearing mice, fluorinated BPA derivatives met the requirements for clinical BNCT even at half of the clinical dose. Thus, fluorinated BPA derivatives are potentially effective boron delivery agents for clinical BNCT in melanoma.


Sujet(s)
Composés benzhydryliques , Thérapie par capture de neutrons par le bore , Halogénation , Animaux , Souris , Thérapie par capture de neutrons par le bore/méthodes , Composés benzhydryliques/composition chimique , Composés benzhydryliques/pharmacologie , Phénols/composition chimique , Phénols/pharmacologie , Humains , Souris de lignée C57BL , Composés du bore/composition chimique , Composés du bore/pharmacologie , Mélanome expérimental/traitement médicamenteux , Mélanome expérimental/anatomopathologie , Structure moléculaire
14.
Org Biomol Chem ; 22(27): 5569-5577, 2024 07 10.
Article de Anglais | MEDLINE | ID: mdl-38887040

RÉSUMÉ

In this paper, two near-infrared BODIPY photosensitizers, Id-BDPI and Cz-BDPI, were obtained by modifying the indole and carbazole aromatic heterocycles in the core of BODIPY. The maximum absorption wavelengths of Id-BDPI and Cz-BDPI were 694 nm and 722 nm, and their singlet oxygen yields were 48% and 48.4%, respectively. In the simulated tumor cell photodynamic therapy, Id-BDPI and Cz-BDPI could effectively inhibit the growth of A549 tumor cells under near-infrared light. Meanwhile, the lysosomal co-localization coefficients of Id-BDPI and Cz-BDPI with A549 tumor cells were 0.94 and 0.89, respectively, showing high lysosomal targeting ability and biocompatibility. The two-photon absorption cross sections measured at 1050 nm by the Z-scanning method were 661.8 GM and 715.6 GM, respectively, and Cz-BDPI was further successfully applied to two-photon fluorescence imaging and two-photon excited singlet oxygen generation in zebrafish. The above results indicate that the introduction of aromatic heterocycles can effectively enhance the photodynamic efficacy of BODIPY photosensitizers, and the larger two-photon absorption cross section also brings potential for two-photon photodynamic therapy applications.


Sujet(s)
Composés du bore , Rayons infrarouges , Photothérapie dynamique , Photons , Photosensibilisants , Oxygène singulet , Danio zébré , Composés du bore/composition chimique , Composés du bore/pharmacologie , Composés du bore/synthèse chimique , Photosensibilisants/pharmacologie , Photosensibilisants/composition chimique , Photosensibilisants/synthèse chimique , Oxygène singulet/métabolisme , Humains , Animaux , Cellules A549 , Antinéoplasiques/pharmacologie , Antinéoplasiques/composition chimique , Antinéoplasiques/synthèse chimique , Structure moléculaire , Tests de criblage d'agents antitumoraux , Prolifération cellulaire/effets des médicaments et des substances chimiques
15.
Org Biomol Chem ; 22(27): 5603-5607, 2024 07 10.
Article de Anglais | MEDLINE | ID: mdl-38904084

RÉSUMÉ

The synthesis of the ethyl ester analogue of the ultrapotent antitumour antibiotic seco-duocarmycin SA has been achieved in eleven linear steps from commercially available starting materials. The DSA alkylation subunit can be made in ten linear steps from the same precursor. The route involves C-H activation at the equivalent of the C7 position on indole leading to a borylated intermediate 9 that is stable enough for peptide coupling reactions but can be easily converted to the free hydroxyl analogue.


Sujet(s)
Duocarmycines , Indoles , Iridium , Catalyse , Indoles/composition chimique , Indoles/synthèse chimique , Iridium/composition chimique , Structure moléculaire , Pyrroles/composition chimique , Pyrroles/synthèse chimique , Composés du bore/composition chimique , Composés du bore/synthèse chimique
16.
Dalton Trans ; 53(27): 11242-11246, 2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-38919991
17.
Anal Chem ; 96(27): 11036-11043, 2024 Jul 09.
Article de Anglais | MEDLINE | ID: mdl-38934556

RÉSUMÉ

Escherichia coli O157:H7 is one of the most susceptible foodborne pathogens, easily causing food poisoning and other health risks. It is of great significance to establish a quantitative method with higher sensitivity and less time consumption for foodborne pathogens analysis. The Raman-silent signal has a good performance for avoiding interference from the food matrix so as to achieve accurate signal differentiation. In this work, we presented a preparation-mapping all-in-one method for digital mapping analysis. We prepared a functionalized Raman-silent polymer label of Escherichia coli O157:H7, which was captured on a porous 4-mercaptophenylboric acid@Ag foam chip. To improve accuracy and widen the detection range, a digital mapping quantitative strategy was employed in data extraction and processing. By transfer mapping information into digitized statistical results, the limitation of obtaining reproducible intensity values just by randomly selected spots on the substrate can be addressed. With a wide linear range of 1.0 × 101-1.0 × 105 CFU mL-1 and a limit of detection of 4.4 CFU mL-1, this all-in-one method had good sensitivity performance. Also, this method achieved good precision and selectivity in a series of experiments and was successfully applied to the analysis of beverage samples.


Sujet(s)
Boissons , Escherichia coli O157 , Polymères , Analyse spectrale Raman , Escherichia coli O157/isolement et purification , Analyse spectrale Raman/méthodes , Boissons/analyse , Boissons/microbiologie , Polymères/composition chimique , Composés du bore/composition chimique , Microbiologie alimentaire/méthodes , Contamination des aliments/analyse , Thiols/composition chimique , Thiols/analyse , Acides boroniques
18.
Int J Biol Macromol ; 273(Pt 2): 132921, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38866281

RÉSUMÉ

In order to investigate the effect of boron element on liquefied wood carbon fibers and their composites, boric acid and boron carbide were utilized to modify liquefied wood resin through copolymerization and blending methods respectively. Then boric acid-modified liquefied wood carbon fiber (BA-WCF) and boron carbide-modified liquefied wood carbon fiber (BC-WCF) were produced via melt spinning, curing, and carbonization treatments. As expected, this modification approach effectively prevents the formation of skin-core structures and accelerates the evolution of a graphite microcrystalline structure, thereby enhancing the mechanical properties of the carbon fibers. Particularly, the tensile strength and elongation at break of BA-WCF increased to 331.57 MPa and 7.57 % respectively, representing increments of 117 % and 86 % compared to the conventional fibers. Furthermore, the as-fabricated carbon fiber/resin composites (CFPRs), composing of BA-WCF or BC-WCF as fillers and liquefied wood resin as matrix, exhibited excellent interlaminar shear strength, outstanding abrasion resistance, and well thermal conductivity, as well as electrical performance, significantly outperforming the conventional carbon fiber/phenolic resin composites. The friction rate of BC-WP/BA-WCF/CF was 2.37 %, while its thermal conductivity could reach 1.927 W/(m·K). These promising attributes lay the groundwork for the development of high-performance carbon fiber-based materials, fostering their widespread utilization across various industries.


Sujet(s)
Fibre de carbone , Conductivité thermique , Bois , Fibre de carbone/composition chimique , Bois/composition chimique , Catalyse , Résistance à la traction , Composés du bore/composition chimique , Acides boriques
19.
Nano Lett ; 24(27): 8287-8295, 2024 Jul 10.
Article de Anglais | MEDLINE | ID: mdl-38941514

RÉSUMÉ

Organic dyes with simultaneously boosted near-infrared-II (NIR-II) fluorescence, type I photodynamic therapy (PDT), and photothermal therapy (PTT) in the aggregate state are still elusive due to the unclear structure-function relationship. Herein, electron-withdrawing substituents are introduced at the 5-indolyl positions of BODIPY dyes to form tight J-aggregates for enhanced NIR-II fluorescence and type I PDT/PTT. The introduction of an electron-rich julolidine group at the meso position and an electron-withdrawing substituent (-F) at the indolyl moiety can enhance intermolecular charge transfer and the hydrogen bonding effect, contributing to the efficient generation of superoxide radicals in the aggregate state. The nanoparticles of BDP-F exhibit NIR-II fluorescence at 1000 nm, good superoxide radical generation ability, and a high photothermal conversion efficiency (50.9%), which enabled NIR-II fluorescence-guided vasculature/tumor imaging and additive PDT/PTT. This work provides a strategy for constructing phototheranostic agents with enhanced NIR-II fluorescence and type I PDT/PTT for broad biomedical applications.


Sujet(s)
Composés du bore , Colorants fluorescents , Photothérapie dynamique , Composés du bore/composition chimique , Composés du bore/usage thérapeutique , Humains , Colorants fluorescents/composition chimique , Animaux , Souris , Nanoparticules/composition chimique , Nanoparticules/usage thérapeutique , Tumeurs/imagerie diagnostique , Tumeurs/thérapie , Lignée cellulaire tumorale , Imagerie optique/méthodes , Photosensibilisants/composition chimique , Photosensibilisants/usage thérapeutique , Thérapie photothermique , Électrons , Rayons infrarouges , Fluorescence
20.
Biomacromolecules ; 25(7): 4215-4232, 2024 Jul 08.
Article de Anglais | MEDLINE | ID: mdl-38845149

RÉSUMÉ

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.


Sujet(s)
Thérapie par capture de neutrons par le bore , Micelles , Thérapie par capture de neutrons par le bore/méthodes , Animaux , Souris , Mélanome expérimental/anatomopathologie , Mélanome expérimental/traitement médicamenteux , Acides boroniques/composition chimique , Lignée cellulaire tumorale , Polyéthylène glycols/composition chimique , Polymères/composition chimique , Souris de lignée C57BL , Esters/composition chimique , Esters/pharmacologie , Composés du bore/composition chimique , Composés du bore/pharmacologie
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