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1.
Angew Chem Int Ed Engl ; : e202414354, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39248101

RESUMEN

While natural channels respond to external stimuli to regulate ion concentration across cell membranes, creating a synthetic version remains challenging. Here, we present a photo-responsive uncaging technique within an artificial ion channel system, which activates the ion transport process from a transport-inactive o-nitrobenzyl-based caged system. From the comparative ion transport screening, 1b emerged as the most active transporter. Interestingly, its bis(o-nitrobenzyl) derivative, i.e., protransporter 1b' was inefficient in transporting ions. Detailed transport studies indicated that compound 1b is an anion selective transporter with a prominent selectivity towards chloride ions by following the antiport mechanism. Compound 1b' did not form an ion channel, but after the o-nitrobenzyl groups were photocleaved, it released 1b, forming a transmembrane ion channel. The channel exhibited an average diameter of 6.5 ± 0.2 Å and a permeability ratio of PCl-/PK+ = 7.3 ± 1.5. The geometry-optimization of protransporter 1b' indicated significant non-planarity, corroborating its inefficient self-assembly. In contrast, the crystal structure of 1b demonstrates strong self-assembly via the formation of an intermolecular H-bond. Geometry optimization studies revealed the plausible self-assembled channel model and the interactions between the channel and chloride ion.

2.
Angew Chem Int Ed Engl ; : e202415250, 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39301990

RESUMEN

Organic phosphorescence glass has garnered considerable attention owing to the excellent shaping ability and photophysical behavior, but facile construction from single-component phosphors is still challenging. Herein, a rigid-soft coupling design is adopted in organic phosphors of ICO, CCO and PCO, thus preparing phosphorescence glasses through melting-quenching method to give excellent shaping ability and dynamic phosphorescence. RTP performance is significantly enhanced in the dense-structure glass, and intriguing high-temperature phosphorescence (HTP) is still observable even at 400 K. Direct patterning under UV irradiation is also achieved using photolithography technique, allowing for the creation of high-quality afterglow patterns that can be reversibly erased and rewritten. This rigid-soft conformation in organic phosphors elucidates a promising concept for achieving efficient RTP glass with wide application prospects.

3.
Biotechniques ; 76(8): 381-393, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39258780

RESUMEN

Modulating autophagy and mitophagy, vital cellular quality control systems, offer therapeutic potential for critical illnesses. However, limited drug screening options hinder progress. We present a novel assay using the photoswitchable fluorescent reporter, mito-Kaede, to quantify mitophagy flux. Mito-Kaede's superior UV-induced photoconversion and brightness post-conversion make it ideal for prolonged mitochondrial dynamics tracking. Its specificity in responding to mitophagy, confirmed by parkin-knockout cells, adds value. When coupled with a custom fluid exchange system, enabling efficient medium changes, precise mitophagy observations become feasible. This mitophagy assay, alongside our methodological insights, can decipher mitophagy's role in pathology and supports drug screening efforts.


Our method introduces a novel systematic approach for chronologically tracking the fluorescent decay of a photoactivatable fluorescent protein, mito-Kaede. This is combined with a fluid-exchange method to enable fixed-point observations before and after mitophagy stimulation.


Asunto(s)
Mitofagia , Humanos , Mitocondrias/metabolismo , Mitocondrias/efectos de la radiación , Células HeLa , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitina-Proteína Ligasas/genética , Colorantes Fluorescentes/química
4.
Toxicol In Vitro ; 100: 105917, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39142446

RESUMEN

Glioblastoma is a malignant neoplasm that develops in the central nervous system and is characterized by high rates of cell proliferation and invasion, presenting resistance to treatments and a poor prognosis. Photodynamic therapy (PDT) is a therapeutic modality that can be applied in oncological cases and stands out for being less invasive. Photosensitizers (PS) of natural origin gained prominence in PDT. Curcumin (CUR) is a natural compound that has been used in PDT, considered a promising PS. In this work, we evaluated the effects of PDT-mediated CUR and near-infrared radiation (NIR) in glioblastoma cells. Through trypan blue exclusion analysis, we chose the concentration of 5 µM of CUR and the dose of 2 J/cm2 of NIR that showed better responses in reducing the viable cell number in the C6 cell line and did not show cytotoxic/cytostatic effects in the HaCat cell line. Our results show that there is a positive interaction between CUR and NIR as a PDT model since there was an increase in ROS levels, a decrease in cell proliferation, increase in cytotoxicity with cell death by autophagy and necrosis, in addition to the presence of oxidative damage to proteins. These results suggest that the use of CUR and NIR is a promising strategy for the antitumor application of PDT.


Asunto(s)
Supervivencia Celular , Curcumina , Glioblastoma , Rayos Infrarrojos , Fotoquimioterapia , Fármacos Fotosensibilizantes , Especies Reactivas de Oxígeno , Curcumina/farmacología , Glioblastoma/tratamiento farmacológico , Humanos , Línea Celular Tumoral , Fármacos Fotosensibilizantes/farmacología , Especies Reactivas de Oxígeno/metabolismo , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Proliferación Celular/efectos de la radiación , Animales , Antineoplásicos/farmacología , Ratas
5.
Wound Repair Regen ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39109695

RESUMEN

Healing of deep cutaneous wounds often results in detrimental sequelae, including painful and debilitating scars. Current therapies for full-thickness injuries that target specific phases of wound healing have moderate success; however, full resolution remains incomplete and negative consequences persist if skin homeostasis is not achieved. Photoactivated molecules can modulate cellular responses by generating reactive oxygen species and may provide a novel therapeutic option to improve wound healing. In the current study, we investigated the effects of Rose bengal (RB) dye in a preclinical model of full-thickness cutaneous injury. Monochromatic green light activates RB to generate ROS in the presence of oxygen, subsequently crosslinking collagen fibrils. In in vitro studies, we show that photoactivated RB is well tolerated by epidermal keratinocytes and dermal fibroblasts and can mitigate fibrotic signalling by downregulating collagen production. In a murine model of full-thickness injury, topically-applied and photoactivated RB closed wounds faster than control and vehicle treatments and showed significantly improved wound healing outcomes, including enhanced early granulation, better collagen organisation and increased vascularity in the presence of protracted tissue ROS. These data support an overall improved cutaneous wound healing profile after RB phototherapy and warrant further investigations into this versatile molecule.

6.
Molecules ; 29(15)2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39125001

RESUMEN

We report on the synthesis of two fluorescent probes which can be activated by ß-Galactosidase (ß-Gal) enzymes and/or light. The probes contained 2-nitro-4-oxybenzyl and 3-nitro-4-oxybenzyl fragments, with ß-Gal residues linked to C-4. We performed the enzymatic and photoactivation of the probes in a cuvette and compared them, prior to the labeling of Vimentin-Halo fusion protein in live cells with overexpressed ß-galactosidase. The dye fluorescence afforded the observation of enzyme activity by means of confocal and super-resolution optical microscopy based on stimulated emission depletion (STED). The tracing of enzymatic activity with the retention of activated fluorescent products inside cells was combined with super-resolution imaging as a tool for use in biomedicine and life science.


Asunto(s)
Colorantes Fluorescentes , beta-Galactosidasa , beta-Galactosidasa/metabolismo , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Humanos , Microscopía Fluorescente/métodos , Coloración y Etiquetado/métodos , Microscopía Confocal , Vimentina/metabolismo
7.
ACS Appl Mater Interfaces ; 16(32): 42794-42801, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39087902

RESUMEN

The development of pure organic room-temperature phosphorescent (RTP) materials greatly facilitates the integrated application of luminescent materials. Herein, a type of photoactivated red RTP material was constructed by simply doping 4-(benzo[c][1,2,5]thiadiazol-5-ylthio)benzonitrile (p-NNS) into a poly(methyl methacrylate) (PMMA) matrix. The obtained film realized a controllable photoactivation process by regulation of diverse solvent levels, demonstrating potential advantages in optical anti-counterfeiting applications. Furthermore, luminescent properties of the doped film were utilized to detect oxygen content from 2.00% to 4.90%, which revealed the exact consumption of ambient oxygen under UV light. Every CIE point of the luminescence corresponds to a certain oxygen content, illustrating the visualization of oxygen content. The remarkable regulation of solvent effect and oxygen content in this work will provide competitive material for further optical applications.

8.
J Cosmet Dermatol ; 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39175423

RESUMEN

BACKGROUND: Photoactivation has been suggested to enhance the efficacy of platelet-rich plasma (PRP) in conditions other than dermatological diseases. AIMS: To evaluate the efficacy of photoactivated PRP (P-PRP) treatment for melasma by comparing it with non-photoactivated, classical PRP (C-PRP). METHODS: The study consisted of 38 female patients diagnosed with melasma between April 2022 and May 2023. The patients were randomized into the P-PRP and C-PRP groups. Three sessions of P-PRP or C-PRP were applied to the patients at 2-week intervals. The Melasma Area and Severity Index (MASI) and Melasma Quality of Life Index (MELASQoL) scores were compared before and 2 weeks after treatment. RESULTS: The median age was 38 years, and the median disease duration was 60 months. Clinically, 94.7% of the cases were centrofacial and 5.3% were malar. According to Wood's lamp examination, 55.3% of the cases were epidermal, 13.2% were dermal, and 31.6% were mixed-type. The median pre- and post-treatment scores were 14.5 and 9, respectively, for MASI and 36.5 and 17, respectively, for MELASQoL. The post-treatment MASI and MELASQoL scores of both groups significantly decreased (p < 0.001 for both). However, the intergroup difference was not significant. When all patients were evaluated together a moderate, positive, and significant relationship was detected between PRP and the pre- and post-treatment MASI and MELASQoL scores (r = 0.494 and p = 0.002). No side effects associated with PRP were observed. CONCLUSION: PRP is an effective and safe treatment method for melasma. Further studies are needed to evaluate the contribution of photoactivation to PRP treatment in melasma.

9.
Front Plant Sci ; 15: 1468763, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39206038
10.
Environ Pollut ; 359: 124578, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39032550

RESUMEN

The photo-activation and photo-dissolution processes of pyrite (FeS2) can affect the environmental behavior of the co-existing hexavalent chromium (Cr(VI)). But the photochemical performance of FeS2 is intimately dependent on its exposed facets. Herein, FeS2 nanosheets (FeS2 NS) and FeS2 nanocubes (FeS2 NC) with the dominant exposed facets of (001) and (210)/(100) respectively are prepared. The more Fe3+, Fe2+, and SO42- are released in the FeS2 NS system than the other system due to its more excellent generation ability of photogenerated electrons and reactive oxygen species. The higher surface energy on (001) facet leads to the faster dissolution rate of FeS2 NS. Due to the optimal production ability of photogenerated electrons and Fe2+ of (001) facet, the much higher Cr(VI) elimination efficiency in the FeS2 NS system is observed than that in the FeS2 NC (72.8%) system within 120 min. This work could help to unveil the influence of FeS2 on the fate of Cr(VI) in surface environment, and offer a theoretical support to clarify the influence of heavy metal ions on the iron sulfide minerals.


Asunto(s)
Cromo , Hierro , Sulfuros , Cromo/química , Sulfuros/química , Hierro/química , Oxidación-Reducción , Procesos Fotoquímicos
11.
Biomater Adv ; 163: 213962, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39032435

RESUMEN

Solid tumors create a hypoxic microenvironment and this character can be utilized for cancer therapy, but the hypoxia levels are insufficient to achieve satisfactory therapeutic benefits. Some tactics have been used to improve hypoxia, which however will cause side effects due to the uncontrolled drug release. We herein report near-infrared (NIR) photoactivatable three-in-one nanoagents (PCT) to aggravate tumor hypoxia and enable amplified photo-combinational chemotherapy. PCT are formed based on a thermal-responsive liposome nanoparticle containing three therapeutic agents: a hypoxia responsive prodrug tirapazamine (TPZ) for chemotherapy, a vascular targeting agent combretastatin A-4 (CA4) for vascular disturbance and a semiconducting polymer for both photodynamic therapy (PDT) and photothermal therapy (PTT). With NIR laser irradiation, PCT generate heat for PTT and destructing thermal-responsive liposomes to achieve activatable releases of TPZ and CA4. Moreover, PCT produce singlet oxygen (1O2) for PDT via consuming tumor oxygen. CA4 can disturb the blood vessels in tumor microenvironment to aggravate the hypoxic microenvironment, which results in the activation of TPZ for amplified chemotherapy. PCT thus enable PTT, PDT and hypoxia-amplified chemotherapy to afford a high therapeutic efficacy to almost absolutely eradicate subcutaneous 4 T1 tumors and effectively inhibit tumor metastases in lung and liver. This work presents an activatable three-in-one therapeutic nanoplatform with remotely controllable and efficient therapeutic actions to treat cancer.


Asunto(s)
Rayos Infrarrojos , Liposomas , Nanopartículas , Fotoquimioterapia , Tirapazamina , Animales , Humanos , Fotoquimioterapia/métodos , Tirapazamina/farmacología , Tirapazamina/química , Tirapazamina/uso terapéutico , Nanopartículas/química , Nanopartículas/uso terapéutico , Ratones , Microambiente Tumoral/efectos de los fármacos , Línea Celular Tumoral , Terapia Fototérmica/métodos , Estilbenos/farmacología , Estilbenos/uso terapéutico , Estilbenos/química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/uso terapéutico , Profármacos/farmacología , Profármacos/química , Profármacos/uso terapéutico , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Hipoxia Tumoral/efectos de los fármacos
12.
ACS Appl Mater Interfaces ; 16(32): 42632-42640, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39082213

RESUMEN

Photoactivation is a phenomenon that could enhance the photoluminescence (PL) and photostability upon UV/vis light exposure, which is usually observed in CdSe/ZnS quantum dots (QDs). However, the photoactivation phenomenon has been scarcely reported in fluorescent carbon quantum dots (CQDs). Herein, the nitrogen-doped carbon quantum dots (N-CQDs) were prepared through a facile solvothermal approach with naphthalenetracarboxylic dianhydride and serine as precursors. Upon simple UV light irradiation for 10 min, the fluorescence quantum yield (QY) of N-CQDs could increase up to 10-fold. Based on this phenomenon, the N-CQDs were explored as an ultraviolet (UV) light sensor to assess the intensity of ultraviolet radiation in sunlight and indirectly evaluate the UV-blocking efficiency of various sunscreen products. Thus, this contribution not only provided an insight into developing a low-cost UV detector but also opened a door for the development of carbon quantum dots with converse-photobleaching properties.

13.
J Hazard Mater ; 476: 134982, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-38917629

RESUMEN

The propagation of antibiotic-resistant bacteria (ARB) and antibiotic resistance genes (ARGs) induced by the release of antibiotics poses great threats to ecological safety and human health. In this study, periodate (PI)/FeS2/simulated sunlight (SSL) system was employed to remove representative ARB, ARGs and antibiotics in water. 1 × 107 CFU mL-1 of gentamycin-resistant Escherichia coli was effectively disinfected below limit of detection in PI/FeS2/SSL system under different water matrix and in real water samples. Sulfadiazine-resistant Pseudomonas and Gram-positive Bacillus subtilis could also be efficiently sterilized. Theoretical calculation showed that (110) facet was the most reactive facet on FeS2 to activate PI for the generation of reactive species (·OH, ·O2-, h+ and Fe(IV)=O) to damage cell membrane and intracellular enzyme defense system. Both intracellular and extracellular ARGs could be degraded and the expression levels of multidrug resistance-related genes were downregulated during the disinfection process. Thus, horizontal gene transfer (HGT) of ARB was inhibited. Moreover, PI/FeS2/SSL system could disinfect ARB in a continuous flow reactor and in an enlarged reactor under natural sunlight irradiation. PI/FeS2/SSL system could also effectively degrade the HGT-promoting antibiotic (ciprofloxacin) via hydroxylation and ring cleavage process. Overall, PI/FeS2/SSL exhibited great promise for the elimination of antibiotic resistance from water.


Asunto(s)
Antibacterianos , Ciprofloxacina , Farmacorresistencia Bacteriana , Compuestos Ferrosos , Ciprofloxacina/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Compuestos Ferrosos/química , Compuestos Ferrosos/farmacología , Farmacorresistencia Bacteriana/genética , Luz Solar , Desinfección/métodos , Purificación del Agua/métodos , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Contaminantes Químicos del Agua , Microbiología del Agua , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/metabolismo , Bacterias/efectos de la radiación , Transferencia de Gen Horizontal
14.
Artículo en Inglés | MEDLINE | ID: mdl-38919078

RESUMEN

Platinum (II) drugs, including cisplatin, carboplatin, and oxaliplatin, have achieved significant clinical success in cancer treatment. However, their clinical application has been greatly hindered by various adverse factors such as non-specific activation and drug resistance. Compared with Pt(II) drugs, the axial ligands within Pt(IV) compounds can improve the pharmacokinetic properties, selectivity, and biological activity, implementing alternative cytotoxic mechanisms beyond DNA cross-linking and partially overcoming drug resistance. The controlled conversion of Pt(IV) prodrugs into Pt(II) agents at the tumor site has been extensively explored internationally. In this review, Pt(IV) prodrug modification strategies are first summarized, next the development of the predominant external and internal photosensitizers is listed. Finally, three representative photoreduction mechanisms and strategies for developing corresponding Pt(IV) prodrugs are discussed. This work provides constructive instruction for the subsequent molecular design of Pt(IV) prodrugs.

.

15.
Chemosphere ; 361: 142549, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38851501

RESUMEN

Titanium dioxide nanoparticles (TiO2-NP) present in wastewater effluent are discharged into freshwater and saltwater (i.e., marine) systems. TiO2-NP can be solar-driven photoactivated by ultraviolet (UV)-light producing reactive oxygen species including hydroxyl radicals (·OH). ·OH are non-selective and react with a broad range of species in water. In other studies, photoactivation of TiO2-NP has been correlated with oxidative stress and ecotoxicological impacts on plant and animal biota. This study examined the photoactivation of TiO2-NP in freshwater and saltwater systems, and contrasted the oxidation potential in both systems using methylene blue (MB) as a reaction probe. Maximum MB loss (51.9%, n = 4; 95% confidence interval 49.4-54.5) was measured in salt-free, deionized water where ·OH scavenging was negligible; minimum MB loss (1%) was measured in saltwater due to significant ·OH scavenging, indicating the inverse correlation between MB loss and radical scavenging. A kinetic analysis of scavenging by seawater constituents indicated Cl- had the greatest impact due to high concentration and high reaction rate constant. Significant loss of MB occurred in the presence of Br- relative to other less aggressive scavengers present in seawater (i.e., HCO3-, HSO4-). This result is consistent with the formation of Bromate, a strong oxidant that subsequently reacts with MB. In freshwater samples collected from different water bodies in Oklahoma (n = 12), the average MB loss was 13.4%. Greater MB loss in freshwater systems relative to marine systems was due to lower ·OH scavenging by various water quality parameters. Overall, TiO2-NP photoactivation in freshwater systems has the potential to cause greater oxidative stress and ecotoxicological impacts than in marine systems where ·OH scavenging is a dominant reaction.


Asunto(s)
Depuradores de Radicales Libres , Agua Dulce , Oxidación-Reducción , Agua de Mar , Titanio , Contaminantes Químicos del Agua , Titanio/química , Titanio/toxicidad , Agua Dulce/química , Agua de Mar/química , Depuradores de Radicales Libres/química , Contaminantes Químicos del Agua/química , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/toxicidad , Radical Hidroxilo/química , Nanopartículas/química , Nanopartículas/toxicidad , Rayos Ultravioleta , Aguas Residuales/química , Azul de Metileno/química
16.
J Exp Bot ; 75(17): 5438-5456, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-38717932

RESUMEN

Plant peptides communicate by binding to a large family of receptor-like kinases (RLKs), and they share a conserved binding mechanism, which may account for their promiscuous interaction with several RLKs. In order to understand the in vivo binding specificity of the CLAVATA3/EMBRYO SURROUNDING REGION-RELATED peptide family in Arabidopsis, we have developed a novel set of CLAVATA3 (CLV3)-based peptide tools. After carefully evaluating the CLE peptide binding characteristics, using solid phase synthesis process, we modified the CLV3 peptide and attached a fluorophore and a photoactivable side group. We observed that the labeled CLV3 shows binding specificity within the CLAVATA1 clade of RLKs while avoiding the distantly related PEP RECEPTOR clade, thus resolving the contradictory results obtained previously by many in vitro methods. Furthermore, we observed that the RLK-bound CLV3 undergoes clathrin-mediated endocytosis and is trafficked to the vacuole via ARA7 (a Rab GTPase)-labeled endosomes. Additionally, modifying CLV3 for light-controlled activation enabled spatial and temporal control over CLE signaling. Hence, our CLV3 macromolecular toolbox can be used to study rapid cell specific down-stream effects. Given the conserved binding properties, in the future our toolbox can also be used as a template to modify other CLE peptides.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Transducción de Señal , Proteínas de Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Arabidopsis/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Unión Proteica , Péptidos/metabolismo
17.
Elife ; 132024 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-38748470

RESUMEN

Acetylcholine is widely believed to modulate the release of dopamine in the striatum of mammals. Experiments in brain slices clearly show that synchronous activation of striatal cholinergic interneurons is sufficient to drive dopamine release via axo-axonal stimulation of nicotinic acetylcholine receptors. However, evidence for this mechanism in vivo has been less forthcoming. Mohebi, Collins and Berke recently reported that, in awake behaving rats, optogenetic activation of striatal cholinergic interneurons with blue light readily evokes dopamine release measured with the red fluorescent sensor RdLight1 (Mohebi et al., 2023). Here, we show that blue light alone alters the fluorescent properties of RdLight1 in a manner that may be misconstrued as phasic dopamine release, and that this artefactual photoactivation can account for the effects attributed to cholinergic interneurons. Our findings indicate that measurements of dopamine using the red-shifted fluorescent sensor RdLight1 should be interpreted with caution when combined with optogenetics. In light of this and other publications that did not observe large acetylcholine-evoked dopamine transients in vivo, the conditions under which such release occurs in behaving animals remain unknown.


Asunto(s)
Neuronas Colinérgicas , Dopamina , Interneuronas , Optogenética , Dopamina/metabolismo , Animales , Interneuronas/metabolismo , Interneuronas/fisiología , Neuronas Colinérgicas/metabolismo , Neuronas Colinérgicas/fisiología , Ratas , Optogenética/métodos , Motivación , Núcleo Accumbens/metabolismo , Núcleo Accumbens/fisiología , Acetilcolina/metabolismo
18.
ACS Appl Bio Mater ; 7(5): 3431-3440, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38697834

RESUMEN

Light-induced release of cisplatin from Pt(IV) prodrugs represents a promising approach for precise control over the antiproliferative activity of Pt-based chemotherapeutic drugs. This method has the potential to overcome crucial drawbacks of conventional cisplatin therapy, such as high general toxicity toward healthy organs and tissues. Herein, we report two Pt(IV) prodrugs with BODIPY-based photoactive ligands Pt-1 and Pt-2, which were designed using carbamate and triazole linkers, respectively. Both prodrugs demonstrated the ability to release cisplatin under blue light irradiation without the requirement of an external reducing agent. Dicarboxylated Pt-2 prodrug turned out to be more stable in the dark and more sensitive to light than its monocarbamate Pt-1 counterpart; these observations were explained using DFT calculations. The investigation of the photoreduction mechanism of Pt-1 and Pt-2 prodrugs using DFT modeling and ΔG0 PET estimation suggests that the photoinduced electron transfer from the singlet excited state of the BODIPY axial ligand to the Pt(IV) center is the key step in the light-induced release of cisplatin from the complexes. Cytotoxicity studies demonstrated that both prodrugs were nontoxic in the dark and toxic to MCF-7 cells under low-dose irradiation with blue light, and the observed effect was solely due to the cisplatin release from the Pt(IV) prodrugs. Our research presents an elegant synthetic approach to light-activated Pt(IV) prodrugs and presents findings that may contribute to the future rational design of photoactivatable Pt(IV) prodrugs.


Asunto(s)
Antineoplásicos , Ensayos de Selección de Medicamentos Antitumorales , Luz , Profármacos , Profármacos/química , Profármacos/farmacología , Profármacos/síntesis química , Humanos , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Estructura Molecular , Ensayo de Materiales , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Cisplatino/farmacología , Cisplatino/química , Tamaño de la Partícula , Compuestos de Boro/química , Compuestos de Boro/farmacología , Compuestos de Boro/síntesis química , Procesos Fotoquímicos , Teoría Funcional de la Densidad
19.
J Proteome Res ; 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713017

RESUMEN

Single-cell proteomics is a powerful approach to precisely profile protein landscapes within individual cells toward a comprehensive understanding of proteomic functions and tissue and cellular states. The inherent challenges associated with limited starting material demand heightened analytical sensitivity. Just as advances in sample preparation maximize the amount of material that makes it from the cell to the mass spectrometer, we strive to maximize the number of ions that make it from ion source to the detector. In isobaric tagging experiments, limited reporter ion generation limits quantitative accuracy and precision. The combination of infrared photoactivation and ion parking circumvents the m/z dependence inherent in HCD, maximizing reporter generation and avoiding unintended degradation of TMT reporter molecules in infrared-tandem mass tags (IR-TMT). The method was applied to single-cell human proteomes using 18-plex TMTpro, resulting in 4-5-fold increases in reporter signal compared to conventional SPS-MS3 approaches. IR-TMT enables faster duty cycles, higher throughput, and increased peptide identification and quantification. Comparative experiments showcase 4-5-fold lower injection times for IR-TMT, providing superior sensitivity without compromising accuracy. In all, IR-TMT enhances the dynamic range of proteomic experiments and is compatible with gas-phase fractionation and real-time searching, promising increased gains in the study of cellular heterogeneity.

20.
Biotechnol J ; 19(5): e2400156, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38804136

RESUMEN

In spite of tremendous efforts dedicated to addressing bacterial infections and biofilm formation, the post-antibiotic ear continues to witness a gap between the established materials and an easily accessible yet biocompatible antibacterial reagent. Here we show carbon dots (CDs) synthesized via a single hydrothermal process can afford promising antibacterial activity that can be further enhanced by exposure to light. By using citric acid and polyethyleneimine as the precursors, the photoluminescence CDs can be produced within a one-pot, one-step hydrothermal reaction in only 2 h. The CDs demonstrate robust antibacterial properties against both Gram-positive and Gram-negative bacteria and, notably, a considerable enhancement of antibacterial effect can be observed upon photo-irradiation. Mechanistic insights reveal that the CDs generate singlet oxygen (1O2) when exposed to light, leading to an augmented reactive oxygen species level. The approach for disruption of biofilms and inhibition of biofilm formation by using the CDs has also been established. Our findings present a potential solution to combat antibacterial resistance and offer a path to reduce dependence on traditional antibiotics.


Asunto(s)
Antibacterianos , Biopelículas , Carbono , Puntos Cuánticos , Biopelículas/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Carbono/química , Carbono/farmacología , Puntos Cuánticos/química , Pruebas de Sensibilidad Microbiana , Especies Reactivas de Oxígeno/metabolismo , Luz , Oxígeno Singlete/metabolismo , Polietileneimina/química , Polietileneimina/farmacología , Ácido Cítrico/química , Ácido Cítrico/farmacología , Bacterias Gramnegativas/efectos de los fármacos
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