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1.
Eur J Pharm Biopharm ; 201: 114366, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38876361

RESUMO

Nanoparticles based on poly(lactic-co-glycolic acid) (PLGA) with various surface chemistry are widely used in biomedicine for theranostic applications. The nature of the external coating of nanoparticles has a significant influence on their efficiency as drug carriers or visualization agents. However, information about the mechanisms of nanoparticle accumulation in tumors and the influence of their surface properties on biodistribution is scarce due to the lack of systematic evaluation. Here we investigate the effect of different polymer coatings of the surface on in vitro and in vivo properties of PLGA nanoparticles. Namely, cell binding efficiency, cytotoxicity, efficiency of fluorescent bioimaging, and tumor accumulation were tested. The highest binding efficiency in vitro and cytotoxicity were observed for positively charged polymers. Interestingly, in vivo fluorescent visualization of tumor-bearing mice and quantitative measurements of biodistribution of magnetite-loaded nanoparticles indicated different dependences of accumulation in tumors on the coating of PLGA nanoparticles. This means that nanoparticle surface properties can simultaneously enhance imaging efficiency and decrease quantitative accumulation in tumors. The obtained data demonstrate the complexity of the dependence of nanoparticles' effectiveness for theranostic applications on surface features. We believe that this study will contribute to the rational design of nanoparticles for effective cancer diagnostics and therapy.


Assuntos
Portadores de Fármacos , Nanopartículas , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Animais , Camundongos , Distribuição Tecidual , Nanopartículas/química , Portadores de Fármacos/química , Humanos , Linhagem Celular Tumoral , Ácido Láctico/química , Propriedades de Superfície , Polímeros/química , Ácido Poliglicólico/química , Feminino
2.
Exp Biol Med (Maywood) ; 249: 10055, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38774281

RESUMO

Currently, various functionalized nanocarrier systems are extensively studied for targeted delivery of drugs, peptides, and nucleic acids. Joining the approaches of genetic and chemical engineering may produce novel carriers for precise targeting different cellular proteins, which is important for both therapy and diagnosis of various pathologies. Here we present the novel nanocontainers based on vectorized genetically encoded Myxococcus xanthus (Mx) encapsulin, confining a fluorescent photoactivatable mCherry (PAmCherry) protein. The shells of such encapsulins were modified using chemical conjugation of human transferrin (Tf) prelabeled with a fluorescein-6 (FAM) maleimide acting as a vector. We demonstrate that the vectorized encapsulin specifically binds to transferrin receptors (TfRs) on the membranes of mesenchymal stromal/stem cells (MSCs) followed by internalization into cells. Two spectrally separated fluorescent signals from Tf-FAM and PAmCherry are clearly distinguishable and co-localized. It is shown that Tf-tagged Mx encapsulins are internalized by MSCs much more efficiently than by fibroblasts. It has been also found that unlabeled Tf effectively competes with the conjugated Mx-Tf-FAM formulations. That indicates the conjugate internalization into cells by Tf-TfR endocytosis pathway. The developed nanoplatform can be used as an alternative to conventional nanocarriers for targeted delivery of, e.g., genetic material to MSCs.


Assuntos
Células-Tronco Mesenquimais , Myxococcus xanthus , Transferrina , Células-Tronco Mesenquimais/metabolismo , Transferrina/metabolismo , Humanos , Myxococcus xanthus/metabolismo , Endocitose , Receptores da Transferrina/metabolismo , Proteínas Luminescentes/metabolismo , Proteínas Luminescentes/genética
3.
Biosensors (Basel) ; 14(5)2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38785689

RESUMO

Graphene-based materials are actively being investigated as sensing elements for the detection of different analytes. Both graphene grown by chemical vapor deposition (CVD) and graphene oxide (GO) produced by the modified Hummers' method are actively used in the development of biosensors. The production costs of CVD graphene- and GO-based sensors are similar; however, the question remains regarding the most efficient graphene-based material for the construction of point-of-care diagnostic devices. To this end, in this work, we compare CVD graphene aptasensors with the aptasensors based on reduced GO (rGO) for their capabilities in the detection of NT-proBNP, which serves as the gold standard biomarker for heart failure. Both types of aptasensors were developed using commercial gold interdigitated electrodes (IDEs) with either CVD graphene or GO formed on top as a channel of liquid-gated field-effect transistor (FET), yielding GFET and rGO-FET sensors, respectively. The functional properties of the two types of aptasensors were compared. Both demonstrate good dynamic range from 10 fg/mL to 100 pg/mL. The limit of detection for NT-proBNP in artificial saliva was 100 fg/mL and 1 pg/mL for rGO-FET- and GFET-based aptasensors, respectively. While CVD GFET demonstrates less variations in parameters, higher sensitivity was demonstrated by the rGO-FET due to its higher roughness and larger bandgap. The demonstrated low cost and scalability of technology for both types of graphene-based aptasensors may be applicable for the development of different graphene-based biosensors for rapid, stable, on-site, and highly sensitive detection of diverse biochemical markers.


Assuntos
Técnicas Biossensoriais , Grafite , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Transistores Eletrônicos , Grafite/química , Fragmentos de Peptídeos/análise , Humanos , Limite de Detecção , Ouro/química , Aptâmeros de Nucleotídeos/química , Eletrodos , Biomarcadores/análise
4.
Int J Mol Sci ; 25(6)2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38542080

RESUMO

Super-enhancers (SEs) are regions of the genome that play a crucial regulatory role in gene expression by promoting large-scale transcriptional responses in various cell types and tissues. Recent research suggests that alterations in super-enhancer activity can contribute to the development and progression of various disorders. The aim of this research is to explore the multifaceted roles of super-enhancers in gene regulation and their significant implications for understanding and treating complex diseases. Here, we study and summarise the classification of super-enhancer constituents, their possible modes of interaction, and cross-regulation, including super-enhancer RNAs (seRNAs). We try to investigate the opportunity of SE dynamics prediction based on the hierarchy of enhancer single elements (enhancers) and their aggregated action. To further our understanding, we conducted an in silico experiment to compare and differentiate between super-enhancers and locus-control regions (LCRs), shedding light on the enigmatic relationship between LCRs and SEs within the human genome. Particular attention is paid to the classification of specific mechanisms and their diversity, exemplified by various oncological, cardiovascular, and immunological diseases, as well as an overview of several anti-SE therapies. Overall, the work presents a comprehensive analysis of super-enhancers across different diseases, aiming to provide insights into their regulatory roles and may act as a rationale for future clinical interventions targeting these regulatory elements.


Assuntos
Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Humanos , Super Intensificadores , RNA
5.
Inorg Chem ; 63(7): 3348-3358, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38320960

RESUMO

Though uranium is usually present in its +6 oxidation state (as uranyl ion) in aqueous solutions, its conversion to oxidation states such as +4 or +5 is a challenging task. Electrochemical reduction and axial oxo activation are the preferred methods to get stable unusual oxidation states of uranium in an aqueous medium. In previous studies, dicarboxylic acid has been used to stabilize UO2+ in aqueous alkaline solutions. In the present work, a diphosphonate ligand was chosen due to its higher complexing ability compared to that of the carboxylate ligands. Neptunium complexation studies with 2,6-pyridinediphosphonic acid (PyPOH) indicated the formation of different species at different pH values and the complexation facilitates disproportionation of NpO2+ to Np4+ and NpO22+ at pH 2. Hexavalent actinides form insoluble complexes in aqueous media at pH = 2, as confirmed by UO22+ complexation studies. The in situ complexation-driven precipitation resulted in conversion to pure Np4+ in aqueous media as the Np4+-PyPOH complex. A strong complexing ability of the PyPOH ligand toward the Np4+ ion is also seen for the stabilization of the electrochemically generated U4+ in aqueous medium under aerobic conditions. The U4+-PyPOH complex was found to be stable for 3 months. Raman, UV-vis, fluorescence, and cyclic voltametric studies along with density functional theory (DFT) calculations were done to get structural insights into the PyPOH complexes of actinides in different oxidation states.

6.
Materials (Basel) ; 17(2)2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38255517

RESUMO

Magnetite nanoparticles (MNPs) are highly favored materials for a wide range of applications, from smart composite materials and biosensors to targeted drug delivery. These multifunctional applications typically require the biofunctional coating of MNPs that involves various conjugation techniques to form stable MNP-biomolecule complexes. In this study, a cost-effective method is developed for the chlorostannate modification of MNP surfaces that provides efficient one-step conjugation with biomolecules. The proposed method was validated using MNPs obtained via an optimized co-precipitation technique that included the use of degassed water, argon atmosphere, and the pre-filtering of FeCl2 and FeCl3 solutions followed by MNP surface modification using stannous chloride. The resulting chlorostannated nanoparticles were comprehensively characterized, and their efficiency was compared with both carboxylate-modified and unmodified MNPs. The biorecognition performance of MNPs was verified via magnetic immunochromatography. Mouse monoclonal antibodies to folic acid served as model biomolecules conjugated with the MNP to produce nanobioconjugates, while folic acid-gelatin conjugates were immobilized on the test lines of immunochromatography lateral flow test strips. The specific trapping of the obtained nanobioconjugates via antibody-antigen interactions was registered via the highly sensitive magnetic particle quantification technique. The developed chlorostannate modification of MNPs is a versatile, rapid, and convenient tool for creating multifunctional nanobioconjugates with applications that span in vitro diagnostics, magnetic separation, and potential in vivo uses.

7.
Phys Chem Chem Phys ; 26(3): 2548-2559, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38170859

RESUMO

A variant of microfluidic setup design for the study of extraction kinetics has been proposed. Mass transfer constants for Am(III) and Eu(III) and observed rate constants were obtained for N-,O-donor ligands featuring phenanthroline and bipyridyl cores. The possibility of determining rate constants for cations independently of each other makes it possible to observe the kinetic effect of separation. The extraction rate was found to be lower for the bipyridyl ligand, compared to phenanthroline. The values of the rotation barriers for the ligands were calculated using the DFT method. The values correlate with the obtained low extraction rate for the bipyridyl ligand. Also, crystallographic data showing anti-conformation for the bipyridyl ligand align with the kinetic data. Surface tension was also determined for the systems with the studied ligands. It is shown that at equal ligand concentrations, the value of surface tension agrees with the extraction rate. Furthermore, it is shown that for the bipyridyl ligand, prior contact of the organic phase with nitric acid significantly affects the surface tension.

8.
Inorg Chem ; 63(1): 602-612, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38112309

RESUMO

The search for new effective extractants is an important task for the management of high-level liquid waste (HLW) generated during the reprocessing of spent nuclear fuel. Here, we synthesized a series of diglycolamides with cyclic substituents for the first time. We disclosed their coordination with f-element nitrates [La(NO3)3 and UO2(NO3)2] by SC-XRD study and complexation properties toward Am(III), Ln(III), and U(VI) during solvent extraction from nitric acid solutions. Using dynamic nuclear magnetic resonance (NMR) and density functional theory (DFT) calculations, the importance of tautomerism in the extraction properties of diglycolamides was shown.

9.
J Am Chem Soc ; 145(46): 25150-25159, 2023 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-37948300

RESUMO

Adaptive and reversible self-assembly of supramolecular protein structures is a fundamental characteristic of dynamic living matter. However, the quantitative detection and assessment of the emergence of mesoscale protein complexes from small and dynamic oligomeric precursors remains highly challenging. Here, we present a novel approach utilizing a short membrane nanotube (sNT) pulled from a planar membrane reservoir as nanotemplates for molecular reconstruction, manipulation, and sensing of protein oligomerization and self-assembly at the mesoscale. The sNT reports changes in membrane shape and rigidity caused by membrane-bound proteins as variations of the ionic conductivity of the sNT lumen. To confine oligomerization to the sNT, we have designed and synthesized rigid oligoamide foldamer tapes (ROFTs). Charged ROFTs incorporate into the planar and sNT membranes, mediate protein binding to the membranes, and, driven by the luminal electric field, shuttle the bound proteins between the sNT and planar membranes. Using Annexin-V (AnV) as a prototype, we show that the sNT detects AnV oligomers shuttled into the nanotube by ROFTs. Accumulation of AnV on the sNT induces its self-assembly into a curved lattice, restricting the sNT geometry and inhibiting the material uptake from the reservoir during the sNT extension, leading to the sNT fission. By comparing the spontaneous and ROFT-mediated entry of AnV into the sNT, we reveal how intricate membrane curvature sensing by small AnV oligomers controls the lattice self-assembly. These results establish sNT-ROFT as a powerful tool for molecular reconstruction and functional analyses of protein oligomerization and self-assembly, with broad application to various membrane processes.


Assuntos
Proteínas de Membrana , Nanotubos , Ligação Proteica , Proteínas de Membrana/metabolismo
10.
Inorg Chem ; 62(43): 17721-17735, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37847197

RESUMO

A highly efficient synthetic approach was developed for the synthesis of unsymmetrical 1,10-phenanthroline-2,9-diamides with two different substituents in the fourth and seventh positions of the phenanthroline core. The structures of these ligands were confirmed using various spectral methods including 2D-NMR and X-ray analysis. Quantum chemical calculations supported the presence of tautomeric forms of these ligands. Furthermore, it was discovered that these compounds exhibit polydentate ligand behavior toward lanthanide nitrates. The structural characteristics of the complexes formed between these ligands and lanthanide nitrates were investigated both in the solid state and in solution. To further understand the binding properties of these novel unsymmetrical ligands, the binding constants for potential complexes were quantitatively measured by using UV-vis spectrophotometric titration. This allowed for a comprehensive analysis of the binding affinity and stability of these complexes. Extraction experiments of f-elements were performed for symmetrical and unsymmetrical diamides. Overall, this study presents significant advancement in the synthesis and characterization of unsymmetrical 1,10-phenanthroline-2,9-diamides and provides valuable insights into their potential applications as polydentate ligands for lanthanide nitrates.

11.
Pharmaceutics ; 15(10)2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37896182

RESUMO

Human glioblastoma multiforme (GBM) is a primary malignant brain tumor, a radically incurable disease characterized by rapid growth resistance to classical therapies, with a median patient survival of about 15 months. For decades, a plethora of approaches have been developed to make GBM therapy more precise and improve the diagnosis of this pathology. Targeted delivery mediated by the use of various molecules (monoclonal antibodies, ligands to overexpressed tumor receptors) is one of the promising methods to achieve this goal. Here we present a novel genetically encoded nanoscale dual-labeled system based on Quasibacillus thermotolerans (Qt) encapsulins exploiting biologically inspired designs with iron-containing nanoparticles as a cargo, conjugated with human fluorescent labeled transferrin (Tf) acting as a vector. It is known that the expression of transferrin receptors (TfR) in glioma cells is significantly higher compared to non-tumor cells, which enables the targeting of the resulting nanocarrier. The selectivity of binding of the obtained nanosystem to glioma cells was studied by qualitative and quantitative assessment of the accumulation of intracellular iron, as well as by magnetic particle quantification method and laser scanning confocal microscopy. Used approaches unambiguously demonstrated that transferrin-conjugated encapsulins were captured by glioma cells much more efficiently than by benign cells. The resulting bioinspired nanoplatform can be supplemented with a chemotherapeutic drug or genotherapeutic agent and used for targeted delivery of a therapeutic agent to malignant glioma cells. Additionally, the observed cell-assisted biosynthesis of magnetic nanoparticles could be an attractive way to achieve a narrow size distribution of particles for various applications.

12.
Dalton Trans ; 52(36): 12934-12947, 2023 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-37646311

RESUMO

In this study, pyridine and phenanthroline diphosphonate ligands were investigated for the first time from the context of solvent extraction and potentiometric sensing of Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and Pb(II) cations. The extraction efficiency under the same conditions for phenanthroline-diphosphonates is considerably higher than that for pyridine ligands. At the same time, the pyridine-diphosphonates show pronounced selectivity towards lead in this metal series. The extraction systems with phenanthroline diphosphonates provided the most efficient extraction of Cd(II) and Pb(II) cations (D > 90). The newly developed pyridine and phenanthroline diphosphonate ligands have proven to be highly effective components in plasticized polymeric membranes. These ligands can be utilized to construct potentiometric ion sensors that exhibit a notable response specifically towards Pb(II) cations. Among the previously reported tetradentate ligands, the phenanthroline diphosphonate ligand, when incorporated into plasticized polymeric membranes, demonstrated the highest sensitivity towards d-metals and Pb(II). The structure of the single crystal complex of Pb(II) and Cd(II) with pyridine-diphosphonates was studied by X-ray diffraction analysis (XRD). The geometry of Cu(II), Zn(II), Cd(II) and Pb(II) complexes and the energy effect of the complex formation, including pseudo-oligomerization reactions, were determined by DFT calculations. The high sensing and extraction efficiency of diphosphonates with respect to Pb(II) is consistent with the minimum values of complex formation energies. The variation in sensory and extraction properties observed among the studied diphosphonate ligands is influenced by the ability to form polynuclear complexes with Pb(II) cations, whereas such properties are absent in the case of Cd(II) cations.

13.
Nanomaterials (Basel) ; 13(14)2023 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-37513041

RESUMO

This study demonstrates the ability to control the properties of TiO2-CuOx composite layers for photocatalytic applications by using a simple electrophoretic deposition method from isopropanol-based suspension. To obtain uniform layers with a controlled composition, the surfactant sodium lauryl sulfate was used, which influenced the electrophoretic mobility of the particles and the morphology of the deposited layers. The TiO2-CuOx composite layers with different CuOx contents (1.5, 5.5, and 11 wt.%) were obtained. It is shown that the optical band gap measured by UV-VIS-NIR diffuse reflectance spectra. When CuOx is added to TiO2, two absorption edges corresponding to TiO2 and CuOx are observed, indicating a broadening of the photosensitivity range of the material relative to pure TiO2. An open-circuit potential study shows that by changing the amount of CuOx in the composite material, one can control the ratio of free charge carriers (n and p) and, therefore, the catalytic properties of the material. As a result, the TiO2-CuOx composite layers have enhanced photocatalytic activity compared to the pure TiO2 layer: methanol yield grows with increasing CuOx content during CO2 photoreduction.

14.
Sensors (Basel) ; 23(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37447898

RESUMO

A comparative study of figure-of-merit fiber sensors of the mass concentration of NaCl solutions based on single-mode and multi-mode fibers was carried out. Lossy mode resonance is realized on chemically thinned sections of optical fibers to various diameters (from 26 to 100 µm) coated with ZnTe. Thin-film coatings were applied using the method of metalorganic chemical vapor deposition (MOCVD). Samples of single-mode and multi-mode fiber sensors were created in such a way that the depth and spectral position of resonances in aqueous NaCl solutions coincided. Sensors implemented on a single-mode fiber have a higher sensitivity (5930 nm/refractive index unit (RIU)) compared to those on a multi-mode fiber (4860 nm/RIU) and a smaller half-width of the resonance in the transmission spectrum. According to the results of experiments, figure-of-merit sensors are in the range of refractive indices of 1.33-1.35 for: multi-mode fiber-25 RIU-1, single-mode fiber-75 RIU-1. The sensitivity of the resulting sensors depends on the surface roughness of the ZnTe coating. The roughness of films synthesized on a single-mode fiber is four times higher than this parameter for a coating on a multi-mode fiber. For the first time, in the transmission spectrum during the synthesis of a thin-film coating on a multi-mode fiber, the possibility of separating the first nine orders of resonances into electric and magnetic transverse components has been demonstrated. The characteristics of sensors with the operating wavelength range in the visible (500-750 nm) and infrared (1350-1550 nm) regions of the spectrum are compared. The characteristics of multi-mode lossy mode resonance sensors are demonstrated, which make them more promising for use in applied devices than for laboratory research.


Assuntos
Fibras Ópticas , Cloreto de Sódio , Refratometria , Água , Eletricidade
15.
Int J Mol Sci ; 24(13)2023 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-37445804

RESUMO

Recent developments in the field of nanomedicine have introduced a wide variety of nanomaterials that are capable of recognizing and killing tumor cells with increased specificity. A major limitation preventing the widespread introduction of nanomaterials into the clinical setting is their fast clearance from the bloodstream via the mononuclear phagocyte system (MPS). One of the most promising methods used to overcome this limitation is the MPS-cytoblockade, which forces the MPS to intensify the clearance of erythrocytes by injecting allogeneic anti-erythrocyte antibodies and, thus, significantly prolongs the circulation of nanoagents in the blood. However, on the way to the clinical application of this approach, the question arises whether the induced suppression of macrophage phagocytosis via the MPS-cytoblockade could pose health risks. Here, we show that highly cytotoxic doxorubicin- or clodronate-loaded liposomes, which are widely used for cancer therapy and biomedical research, induce a similar increase in the nanoparticle blood circulation half-life in mice as the MPS-cytoblockade, which only gently and temporarily saturates the macrophages with the organism's own erythrocytes. This result suggests that from the point of view of in vivo macrophage suppression, the MPS-cytoblockade should be less detrimental than the liposomal anti-cancer drugs that are already approved for clinical application while allowing for the substantial improvement in the nanoagent effectiveness.


Assuntos
Antineoplásicos , Nanopartículas , Camundongos , Animais , Lipossomos , Ácido Clodrônico/farmacologia , Sistema Fagocitário Mononuclear , Antineoplásicos/farmacologia , Doxorrubicina/farmacologia
16.
Int J Mol Sci ; 24(12)2023 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-37373410

RESUMO

A reaction of acyl chlorides derived from 1,10-phenanthroline-2,9-dicarboxylic acids with piperazine allows the preparation of the corresponding 24-membered macrocycles in good yield. The structural and spectral properties of these new macrocyclic ligands were thoroughly investigated, revealing promising coordination properties towards f-elements (Am, Eu). It was shown that the prepared ligands can be used for selective extraction of Am(III) from alkaline-carbonate media in presence of Eu(III) with an SFAm/Eu up to 40. Their extraction efficiency is higher than calixarene-type extraction of the Am(III) and Eu(III) pair. Composition of macrocycle-metal complex with Eu(III) was investigated by luminescence and UV-vis spectroscopy. The possibility of such ligands to form complexes of L:Eu = 1:2 stoichiometry is revealed.


Assuntos
Complexos de Coordenação , Diamida , Modelos Moleculares , Ligantes , Complexos de Coordenação/química
17.
Cells ; 12(8)2023 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-37190100

RESUMO

Super-enhancers (SEs) are cis-regulatory elements of the human genome that have been widely discussed since the discovery and origin of the term. Super-enhancers have been shown to be strongly associated with the expression of genes crucial for cell differentiation, cell stability maintenance, and tumorigenesis. Our goal was to systematize research studies dedicated to the investigation of structure and functions of super-enhancers as well as to define further perspectives of the field in various applications, such as drug development and clinical use. We overviewed the fundamental studies which provided experimental data on various pathologies and their associations with particular super-enhancers. The analysis of mainstream approaches for SE search and prediction allowed us to accumulate existing data and propose directions for further algorithmic improvements of SEs' reliability levels and efficiency. Thus, here we provide the description of the most robust algorithms such as ROSE, imPROSE, and DEEPSEN and suggest their further use for various research and development tasks. The most promising research direction, which is based on topic and number of published studies, are cancer-associated super-enhancers and prospective SE-targeted therapy strategies, most of which are discussed in this review.


Assuntos
Elementos Facilitadores Genéticos , Neoplasias , Humanos , Elementos Facilitadores Genéticos/genética , Estudos Prospectivos , Reprodutibilidade dos Testes , Neoplasias/genética , Carcinogênese/genética
18.
MethodsX ; 10: 102165, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37091956

RESUMO

Many papers offer methods for preparing a systematic literature review. These methods assume that the researchers have some experience in research, are proficient in English, and that the research objective is solely a literature review. This article presents a systematic method for preparing a literature review aimed at novice researchers who have four to twelve weeks to develop their work and do not have the guidance of a professor. Originality is associated with the objective of the literature review. The proposed method aims to elaborate the literature section of a technical article, while the other methods aim to elaborate a literature review article. The method's flexible structure allows for increasing the depth of the results according to the researcher's capacity. Another innovation of the presented method consists of a structure that allows the simultaneous consideration of international and national literature.•This paper introduces a systematized method to guide novice researchers in preparing the literature review section of their research.•The method has an easy-to-follow structure that does not require the novice researcher to follow up with a professor.•The method allows adjusting the depth level of the international literature review through the number of articles subject to content analysis, exploring the international and national literature through a set of materials (graphs, forms, and figures) that facilitate and speed up the elaboration, synthesis, and presentation of the results.

19.
Molecules ; 28(8)2023 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-37110552

RESUMO

The therapeutic potential of short interfering RNA (siRNA) to treat many diseases that are incurable with traditional preparations is limited by the extensive metabolism of serum nucleases, low permeability through biological membrane barriers because of a negative charge, and endosomal trapping. Effective delivery vectors are required to overcome these challenges without causing unwanted side effects. Here, we present a relatively simple synthetic protocol to obtain positively charged gold nanoparticles (AuNPs) with narrow size distribution and the surface modified with Tat-related cell-penetrating peptide. The AuNPs were characterized using TEM and the localized surface plasmon resonance technique. The synthesized AuNPs showed low toxicity in experiments in vitro and were able to effectively form complexes with double-stranded siRNA. The obtained delivery vehicles were used for intracellular delivery of siRNA in an ARPE-19 cell line transfected with secreted embryonic alkaline phosphatase (SEAP). The delivered oligonucleotide remained intact and caused a significant knockdown effect on SEAP cell production. The developed material could be useful for delivery of negatively charged macromolecules, such as antisense oligonucleotides and various RNAs, particularly for retinal pigment epithelial cell drug delivery.


Assuntos
Ouro , Nanopartículas Metálicas , RNA Interferente Pequeno/metabolismo , Ouro/química , Nanopartículas Metálicas/química , RNA de Cadeia Dupla , Sistemas de Liberação de Medicamentos
20.
Int J Mol Sci ; 24(6)2023 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-36982643

RESUMO

Three pyrrolidine-derived phenanthroline diamides were studied as ligands for lutetium trinitrate. The structural features of the complexes have been studied using various spectral methods and X-ray. The presence of halogen atoms in the structure of phenanthroline ligands has a significant impact on both the coordination number of lutetium and the number of solvate water molecules in the internal coordination sphere. The stability constants of complexes with La(NO3)3, Nd(NO3)3, Eu(NO3)3, and Lu(NO3)3 were measured to demonstrate higher efficiency of fluorinated ligands. NMR titration was performed for this ligand, and it was found that complexation with lutetium leads to an approximately 13 ppm shift of the corresponding signal in the 19F NMR spectrum. The possibility of formation of a polymeric oxo-complex of this ligand with lutetium nitrate was demonstrated. Experiments on the liquid-liquid extraction of Am(III) and Ln(III) nitrates were carried out to demonstrate advantageous features of chlorinated and fluorinated pyrrolidine diamides.


Assuntos
Flúor , Fenantrolinas , Modelos Moleculares , Fenantrolinas/química , Ligantes , Diamida , Lutécio , Fluoretos , Pirrolidinas , Solventes
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