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1.
Talanta ; 274: 125975, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38599114

RESUMO

Sirtuin1 (SIRT1), an NAD+-dependent histone deacetylase, plays a crucial role in regulating molecular signaling pathways. Recently, inhibition of SIRT1 rather than its activation shows the therapeutic potential for central nervous system disorder, however, the discovered SIRT1 inhibitors remains limited. In this work, a dual recognition-based strategy was developed to screen SIRT1 inhibitors from natural resources in situ. This approach utilized a Ni-modified metal-organic framework (Ni@Tyr@UiO-66-NH2) along with cell lysate containing an engineered His-tagged SIRT1 protein, eliminating the need for purified proteins, pure compounds, and protein immobilization. The high-performance Ni@Tyr@UiO-66-NH2 was synthesized by modifying the surface of UiO-66-NH2 with Ni2+ ions to specifically capture His-tagged SIRT1 while persevering its enzyme activity. By employing dual recognition, in which Ni@Tyr@UiO-66-NH2 recognized SIRT1 and SIRT1 recognized its ligands, the process of identifying SIRT1 inhibitors from complex matrix was vastly streamlined. The developed method allowed the efficient discovery of 16 natural SIRT1 inhibitors from Chinese herbs. Among them, 6 compounds were fully characterized, and suffruticosol A was found to have an excellent IC50 value of 0.95 ±â€¯0.12 µM. Overall, an innovative dual recognition-based strategy was proposed to efficiently identify SIRT1 inhibitors in this study, offering scientific clues for the development of drugs targeting CNS disorders.


Assuntos
Medicamentos de Ervas Chinesas , Estruturas Metalorgânicas , Níquel , Sirtuína 1 , Sirtuína 1/antagonistas & inibidores , Sirtuína 1/metabolismo , Níquel/química , Estruturas Metalorgânicas/química , Humanos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Avaliação Pré-Clínica de Medicamentos
2.
J Chromatogr A ; 1722: 464911, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38626541

RESUMO

In this study, we have synthesised a chiral l-hyp-Ni/Fe@SiO2 composite as a chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC) for the first time. This was achieved by coating two-dimensional (2D) chiral metal-organic framework nanosheets (MONs) l-hyp-Ni/Fe onto the surface of activated SiO2 microspheres using the "wrapped in net" method. The separation efficiency of the l-hyp-Ni/Fe chromatographic column was systematically evaluated in normal-phase HPLC (NP-HPLC) and reversed-phase HPLC (RP-HPLC) configurations, employing various racemates as analytes. The findings revealed that 16 chiral compounds were separated using NP-HPLC, and five were separated using RP-HPLC, encompassing alcohols, amines, ketones, esters, alkanes, ethers, amino acids and sulfoxides. Notably, the resolution (Rs) of nine chiral compounds exceeded 1.5, indicating baseline separation. Furthermore, the resolution performance of the l-hyp-Ni/Fe@SiO2-packed column was compared with that of Chiralpak AD-H. It was observed that certain enantiomers, which either could not be resolved or were inadequately separated on the Chiralpak AD-H column, attained separation on the 2D chiral MONs column. These findings suggest a complementary relationship between the two columns in racemate separation, with their combined application facilitating the resolution of a broader spectrum of chiral compounds. In addition, baseline separation was achieved for five positional isomers on the l-hyp-Ni/Fe@SiO2-packed column. The effects of the analyte mass and column temperature on the resolution were also examined. Moreover, during HPLC analysis, the l-hyp-Ni/Fe columns demonstrated commendable repeatability, stability and reproducibility in enantiomer separation. This research not only advances the utilisation of 2D chiral MONs as CSPs but also expands their applications in the separation sciences.


Assuntos
Estruturas Metalorgânicas , Dióxido de Silício , Cromatografia Líquida de Alta Pressão/métodos , Dióxido de Silício/química , Estruturas Metalorgânicas/química , Estereoisomerismo , Nanoestruturas/química , Ferro/química , Níquel/química
3.
Adv Healthc Mater ; 13(17): e2303842, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38458147

RESUMO

Although being applied as photosensitizers for photodynamic therapy, covalent organic frameworks (COFs) fail the precise fluorescence imaging in vivo and phototherapy in deep-tissue, due to short excitation/emission wavelengths. Herein, this work proposes the first example of NIR-II emissive and benzobisthiadiazole-based COF-980. Comparing to its ligands, the structure of COF-980 can more efficiently reducing the energy gap (ΔES1-T1) between the excited state and the triplet state to enhance photodynamic therapy efficiency. Importantly, COF-980 demonstrates high photostability, good anti-diffusion property, superior reactive oxygen species (ROS) generation efficiency, promising imaging ability, and ROS production in deep tissue (≈8 mm). Surprisingly, COF-980 combined with laser irradiation could trigger larger amount of intracellular ROS to high efficiently induce cancer cell death. Notably, COF-980 NPs precisely enable PDT guided by NIR-II fluorescence imaging that effectively inhibit the 4T1 tumor growth with negligible adverse effects. This study provides a universal approach to developing long-wavelength emissive COFs and exploits its applications for biomedicine.


Assuntos
Imagem Óptica , Fotoquimioterapia , Espécies Reativas de Oxigênio , Tiadiazóis , Fotoquimioterapia/métodos , Tiadiazóis/química , Tiadiazóis/farmacologia , Animais , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Imagem Óptica/métodos , Linhagem Celular Tumoral , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Camundongos Endogâmicos BALB C , Feminino
4.
ACS Appl Mater Interfaces ; 16(11): 14296-14307, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38452344

RESUMO

Porous iron(III) carboxylate metal-organic frameworks (MIL-100; MIL stands for Material of Institute Lavoisier) of submicronic size (nanoMOFs) have attracted a growing interest in the field of drug delivery due to their high drug payloads, excellent entrapment efficiencies, biodegradable character, and poor toxicity. However, only a few studies have dealt with the nanoMOF degradation mechanism, which is key to their biological applications. Complementary methods have been used here to investigate the degradation mechanism of Fe-based nanoMOFs under neutral or acidic conditions and in the presence of albumin. High-resolution STEM-HAADF coupled with energy-dispersive X-ray spectroscopy enabled the monitoring of the crystalline organization and elemental distribution during degradation. NanoMOFs were also deposited onto silicon substrates by dip-coating, forming stable thin films of high optical quality. The mean film thickness and structural changes were further monitored by IR ellipsometry, approaching the "sink conditions" occurring in vivo. This approach is essential for the successful design of biocompatible nano-vectors under extreme diluted conditions. It was revealed that while the presence of a protein coating layer did not impede the degradation process, the pH of the medium in contact with the nanoMOFs played a major role. The degradation of nanoMOFs occurred to a larger extent under neutral conditions, rapidly and homogeneously within the crystalline matrices, and was associated with the departure of their constitutive organic ligand. Remarkably, the nanoMOFs' particles maintained their global morphology during degradation.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Estruturas Metalorgânicas/química , Compostos Férricos/química , Nanopartículas/química , Sistemas de Liberação de Medicamentos , Ferro/química
5.
Acta Biomater ; 178: 296-306, 2024 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-38417646

RESUMO

Manipulation of the lactate metabolism is an efficient way for cancer treatment given its involvement in cancer development, metastasis, and immune escape. However, most of the inhibitors of lactate transport carriers suffer from poor specificity. Herein, we use the CRISPR/Cas9 system to precisely downregulate the monocarboxylate carrier 1 (MCT1) expression. To avoid the self-repairing during the gene editing process, a dual-Cas9 ribonucleoproteins (duRNPs) system is generated using the biological fermentation method and delivered into cells by the zeolitic imidazolate framework-8 (ZIF-8) nanoparticles, enabling precise removal of a specific DNA fragment from the genome. For efficient cancer therapy, a specific glucose transporter 1 inhibitor (BAY-876) is co-delivered with the duRNPs, forming BAY/duRNPs@ZIF-8 nanoparticle. ZIF-8 nanoparticles can deliver the duRNPs into cells within 1 h, which efficiently downregulates the MCT1 expression, and prohibits lactate influx. Through simultaneous inhibition of the lactate and glucose influx, BAY/duRNPs@ZIF-8 prohibits ATP generation, arrests cell cycle, inhibits cell proliferation, and finally induces cellular apoptosis both in vitro and in vivo. Consequently, we demonstrate that the biologically produced duRNPs delivered into cells by the nonviral ZIF-8 carrier have expanded the CRISPR/Cas gene editing toolbox and elevated the gene editing efficiency, which will promote biological studies and clinical applications. STATEMENT OF SIGNIFICANCE: The CRISPR/Cas9 system, widely used as an efficient gene editing tool, faces a challenge due to cells' ability to self-repair. To address this issue, a strategy involving dual-cutting of the genome DNA has been designed and implemented. This strategy utilizes biologically produced dual-ribonucleoproteins delivered by a metal-organic framework. The effectiveness of this dual-cut CRISPR-Cas9 system has been demonstrated through a therapeutic approach targeting the simultaneous inhibition of lactate and glucose influx in cancer cells. The utilization of the dual-cut gene editing strategy has provided valuable insights into gene editing and expanded the toolbox of the CRISPR/Cas-based gene editing system. It has the potential to enable more efficient and precise manipulation of specific protein expression in the future.


Assuntos
Estruturas Metalorgânicas , Neoplasias , Edição de Genes/métodos , Sistemas CRISPR-Cas/genética , DNA , Ribonucleoproteínas/genética , Lactatos , Glucose , Neoplasias/genética , Neoplasias/terapia
6.
ACS Nano ; 18(8): 6533-6549, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38355215

RESUMO

Conventional agrochemicals are underutilized due to their large particle sizes, poor foliar retention rates, and difficult translocation in plants, and the development of functional nanodelivery carriers with high adhesion to the plant body surface and efficient uptake and translocation in plants remains challenging. In this study, a nanodelivery system based on a pectin-encapsulated iron-based MOF (TF@Fe-MOF-PT NPs) was constructed to enhance the utilization of thifluzamide (TF) in rice plants by taking advantage of the pectin affinity for plant cell walls. The prepared TF@Fe-MOF-PT NPs exhibited an average particle size of 126.55 nm, a loading capacity of 27.41%, and excellent dual-stimulus responses to reactive oxygen species and pectinase. Foliar washing experiments showed that the TF@Fe-MOF-PT NPs were efficiently adhered to the surfaces of rice leaves and stems. Confocal laser scanning microscopy showed that fluorescently labeled TF@Fe-MOF-PT NPs were bidirectionally delivered through vascular bundles in rice plants. The in vitro bactericidal activity of the TF@Fe-MOF-PT NPs showed better inhibitory activity than that of a TF suspension (TF SC), with an EC50 of 0.021 mg/L. A greenhouse test showed that the TF@Fe-MOF-PT NPs were more effective than TF SC at 7 and 14 d, with control effects of 85.88 and 78.59%, respectively. It also reduced the inhibition of seed stem length and root length by TF SC and promoted seedling growth. These results demonstrated that TF@Fe-MOF-PT NPs can be used as a pesticide nanodelivery system for efficient delivery and intelligent release in plants and applied for sustainable control of pests and diseases.


Assuntos
Fungicidas Industriais , Estruturas Metalorgânicas , Nanopartículas , Ferro , Fungicidas Industriais/farmacologia , Pectinas
7.
Food Chem ; 445: 138747, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38387317

RESUMO

A new 3D metal-organic framework {[Cd16(tr2btd)10(dcdps)16(H2O)3(EtOH)]∙15DMF}n (MOF 1, tr2btd = 4,7-di(1,2,4-triazol-1-yl)benzo-2,1,3-thiadiazole, H2dcdps = 4,4'-sulfonyldibenzoic acid) was obtained and its luminescent properties were studied. MOF 1 exhibited bright blue-green luminescence with a high quantum yield of 74 % and luminescence quenching response to a toxic natural polyphenol gossypol and luminescence enhancement response to some trivalent metal cations (Fe3+, Cr3+, Al3+ and Ga3+). The limit of gossypol detection was 0.20 µM and the determination was not interfered by the components of the cottonseed oil. The limit of detection of gallium(III) was 1.1 µM. It was demonstrated that MOF 1 may be used for distinguishing between the genuine sunflower oil and oil adulterated by crude cottonseed oil through qualitative luminescent and quantitative visual gossypol determination.


Assuntos
Gálio , Gossipol , Estruturas Metalorgânicas , Petróleo , Óleo de Sementes de Algodão , Luminescência , Culinária
8.
Environ Sci Pollut Res Int ; 31(14): 20999-21011, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38379044

RESUMO

The reduction of soluble U(VI) to insoluble and less toxic U(IV) by photocatalysis is an effective method to control uranium contamination. The graphitic carbon nitride nanosheet (CNN)/UiO-66 composites (CNNU) were prepared by thermal polymerization and solvothermal methods for the removal of U(VI). The morphology, crystal structure and optical properties of composites were analyzed by SEM, XRD, BET, UV-DRS, PL and EIS. The results showed the introduction of UiO-66 increased the specific surface of CNN from 9.07 m2/g to 46.24 m2/g, and effectively suppressed the recombination of photogenerated electrons and holes and improved the photocatalytic activity. The U(VI) removal capacity by adsorption and photocatalysis of CNNU was reached 779.47 mg/g, which significantly higher than that of adsorption (478.38 mg/g). The adsorption process was found to conform to the pseudo-second-order kinetic model and the Langmuir isothermal model. Meanwhile, U(VI) adsorbed on the CNNU was reduced to U(IV) via e- and ·O2- generated in the photocatalytic process. Therefore, this outstanding performance of CNNU in U(VI) removal is attributed to the synergistic effect of adsorption and photocatalytic reduction.


Assuntos
Estruturas Metalorgânicas , Ácidos Ftálicos , Urânio , Adsorção , Urânio/química , Luz Solar
9.
Int J Biol Macromol ; 262(Pt 1): 130013, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38340930

RESUMO

A natural polysaccharide-based vehicle is facilely prepared for enantioselective loading of S-naproxen (S-NPX) and its programmed release. Cyclodextrin metal-organic frameworks (CD-MOF) are synthesized through the coordination of K+ with γ-cyclodextrin (γ-CD). Compared with R-NPX, the CD-MOF preferably combines with S-NPX, which can be confirmed by the thermodynamic calculations. The S-NPX loaded CD-MOF (CD-MOF-S-NPX) is grafted with disulfide bond (-S-S-) to improve its hydrophobicity, and the loaded S-NPX is further encapsulated in the chiral cavity of γ-CD by carboxymethyl potato starch (CPS) hydrogels. The intermolecular hydrogen bonding of the CPS hydrogels is prone to be destroyed in mildly basic media (∼pH 8.0), resulting in the swelling of the hydrogels; the -S-S- linkage in the vehicle can be cleaved in the presence of glutathione (GSH), leading to the collapse of the CD-MOF. Therefore, the programmed release of S-NPX can be achieved. Also in this work, the release kinetics is investigated, and the results indicate that the release of S-NPX is controlled by the Higuchi model.


Assuntos
Ciclodextrinas , Estruturas Metalorgânicas , Solanum tuberosum , Ciclodextrinas/química , Naproxeno/química , Estruturas Metalorgânicas/química , Hidrogéis , Estereoisomerismo
10.
Anal Chim Acta ; 1295: 342328, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38355226

RESUMO

Enzyme cascade with high specificity and catalytic efficiency has significant applications for developing efficient bioanalysis methods. In this work, a sensitive and selective aptasensor was constructed based on the DNA-induced assembly of biocatalytic nanocompartments. Different from the conventional co-immobilization in one pot, the cascade enzymes of glucose oxidase (GOX) and horseradish peroxidase (HRP) were separately encapsulated in ZIF-90 nanoparticles. After conjugating complementary DNA or aptermer on enzyme@ZIF-90, DNA hybridization drove enzyme@ZIF-90 connected into clusters or linked on other DNA modified biocatalytic nanocompartment (such as invertase loaded Fe3O4@SiO2). Owing to the shortened distance between enzymes, the catalytic efficiency of connected clusters was significantly enhanced. However, the specifically interaction between the substrate molecule and aptermer sequence would lead to the disassembly of DNA duplexes, resulting in the gradual "switching-off" of cascade reactions. With aflatoxin B1 (AFB1) as the model substrate, the compartmentalized three-enzyme nanoreactors showed good analytical performance in the linear range from 0.01 ng mL-1 to 50 ng mL-1 with a low detection limit (3.3 pg mL-1). In addition, the proposed aptasensor was applied to detect AFB1 in corn oil and wheat powder samples with total recoveries ranging from 94 % to 109 %. As a result, this DNA-induced strategy for enzyme cascade nanoreactors opens new avenues for stimuli-responsive applications in biosensing.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , Estruturas Metalorgânicas , Nanopartículas , Aflatoxina B1/análise , Dióxido de Silício/química , DNA/química , Nanopartículas Metálicas/química , Técnicas Biossensoriais/métodos , Limite de Detecção , Aptâmeros de Nucleotídeos/química
11.
Mikrochim Acta ; 191(1): 70, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-38165510

RESUMO

A smartphone-assisted, paper-based ratio fluorescence probe is presented for the rapid, low-cost and on-site quantification of total flavonol glycosides in Ginkgo biloba extracts (GBE). The Al3+/Eu-MOF/paper-based probe utilizes lanthanide metal-organic framework (Ln-MOF) nanoparticles immobilized on Whatman filter paper along with Al3+ for detecting flavonols, which are the hydrolyzed products of flavonol glycosides. The color change of the paper-based fluorescence image from red to orange depends on the concentration of the target analyte in the sample solution. The smartphone equipped with a red, green, blue (RGB) color detector measured the fluorescence signal intensity on the paper substrate after adding flavonol. The analytical variables affecting the performance of the probe, including the addition sequence of the aluminum nitrate solution, its concentration, that of the Ln-MOF solution, the drying time of the paper probe, the reaction time and the sensitivity parameters of the mobile phone camera (ISO), were optimized. Under optimal conditions, the Al3+/Eu-MOF/paper-based probe has good linear response in the concentration range 7 ~ 80 µg mL- 1 and a lower detection limit of 2.07 µg mL- 1. The results obtained with the paper-based ratio fluorescence probe and smartphone combination were validated by comparing them with high-performance liquid chromatography (HPLC) measurements. This study provides a potential strategy for fabricating Al3+/Eu-MOF/paper-based probe used for total flavonol glycosides determination.


Assuntos
Elementos da Série dos Lantanídeos , Estruturas Metalorgânicas , Smartphone , Diagnóstico por Imagem , Flavonóis , Glicosídeos , Extratos Vegetais
12.
Environ Sci Pollut Res Int ; 31(9): 13270-13283, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38243029

RESUMO

The seed germination, as well as root and shoot growth effect of HKUST-1 MOF, and its derived linear polymer ([Cu2(OH)(BTC)(H2O)]n·2nH2O) were herein examined. These effects were studied for seven higher plant species: sweet corn (Zea mays L.), black bean (Phaseolus vulgaris L.), tomato (Solanum lycopersicum L.), lettuce (Lactuca sativa L.), celosia (Celosia argentea L.), Aztec marigold (Tagetes erecta L.), and gypsophila (Gypsophila paniculata L.). The studied concentrations of MOFs were 10, 100, 500, or 1000 mg/L, enhancing the percentage of germination and growth of plants in most species. In general, the growth of the root is lower compared to the controls due to the capacity of the MOF to adsorb water and provide micronutrients such as C, O, and Cu, acting as a reserve for the plant. Shoot system growths are more pronounced with HKUST-1 compared with control, and linear polymer, due to the 3D structure adsorbs major water contents. It was found that all studied species are tolerant not only to Cu released from the material, but more evident to Cu structured in MOFs, and this occurs at high concentrations compared to many other systems. Finally, copper fixation was not present, studied by EDX mapping, banning the possibility of metallic phytotoxicity to the tested cultivars.


Assuntos
Germinação , Estruturas Metalorgânicas , Cobre/farmacologia , Sementes , Plantas , Lactuca , Água
13.
Int J Biol Macromol ; 260(Pt 2): 129391, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38242413

RESUMO

The nanotechnology is an interdisciplinary field that has become a hot topic in cancer therapy. Metal-organic frameworks (MOFs) are porous materials and hybrid composites consisted of organic linkers and metal cations. Despite the wide application of MOFs in other fields, the potential of MOFs for purpose of cancer therapy has been revealed by the recent studies. High surface area and porosity, significant drug loading and encapsulation efficiency are among the benefits of using MOFs in drug delivery. MOFs can deliver genes/drugs with selective targeting of tumor cells that can be achieved through functionalization with ligands. The photosensitizers and photo-responsive nanostructures including carbon dots and gold nanoparticles can be loaded in/on MOFs to cause phototherapy-mediated tumor ablation. The immunogenic cell death induction and increased infiltration of cytotoxic CD8+ and CD4+ T cells can be accelerated by MOF platforms in providing immunotherapy of tumor cells. The stimuli-responsive MOF platforms responsive to pH, redox, enzyme and ion can accelerate release of therapeutics in tumor site. Moreover, MOF nanocomposites can be modified ligands and green polymers to improve their selectivity and biocompatibility for cancer therapy. The application of MOFs for the detection of cancer-related biomarkers can participate in the early diagnosis of patients.


Assuntos
Nanopartículas Metálicas , Estruturas Metalorgânicas , Nanocompostos , Neoplasias , Humanos , Estruturas Metalorgânicas/química , Ouro , Biomimética , Fototerapia , Sistemas de Liberação de Medicamentos , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Nanocompostos/uso terapêutico
14.
Int J Pharm ; 652: 123811, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38237709

RESUMO

Nanoformulations for combining chemotherapy, chemodynamic therapy, and photothermal therapy have enormous potential in tumor treatment. Coating nanoformulations with cell membranes endows them with homologous cellular mimicry, enabling nanoformulations to acquire new functions and properties, including homologous targeting and long circulation in vivo, and can enhance internalization by homologous cancer cells. Herein, we fused multifunctional biomimetic nanoformulations based on Cu-doped zeolitic imidazolate framework-8 (ZIF-8). Hydroxycamptothecin (HCPT), a clinical anti-tumor drug, was encapsulated into ZIF-8, which was subsequently coated with polydopamine (PDA) and red blood cell membrane. The as-fabricated biomimetic nanoformulations showed an enhanced cell uptake in vitro and the potential to prolong blood circulation in vivo, producing effective synergistic chemotherapy, chemodynamic therapy, and photothermal therapy under the 808 nm laser irradiation. Together, the biomimetic nanoformulations showed a prolonged blood circulation and evasion of immune recognition in vivo to provide a bio-inspired strategy which may have the potential for the multi-synergistic therapy of breast cancer.


Assuntos
Estruturas Metalorgânicas , Nanopartículas , Neoplasias , Humanos , Terapia Fototérmica , Doxorrubicina , Biomimética , Fototerapia , Nanopartículas/uso terapêutico , Neoplasias/tratamento farmacológico , Eritrócitos
15.
Colloids Surf B Biointerfaces ; 234: 113707, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38181689

RESUMO

Activated M1-type macrophages, which produce inflammatory factors that exacerbate rheumatoid arthritis (RA), represent crucial target cells for inhibiting the disease process. In this study, we developed a novel photoresponsive targeted drug delivery system (TPNPs-HA) that can effectively deliver the hypoxia-activated prodrug tirapazamine (TPZ) specifically to activated macrophages. After administration, this metal-organic framework, PCN-224, constructed uing the photosensitizer porphyrin, exhibits the ability to generate excessive toxic reactive oxygen species (ROS) when exposed to near-infrared light. Additionally, the oxygen-consumed hypoxic environment further activates the chemotherapeutic effect of TPZ, thus creating a synergistic combination of photodynamic therapy (PDT) and hypoxia-activated chemotherapy (HaCT) to promote the elimination of activated M1-type macrophages. The results highlight the significantly potential of this photoresponsive nano-delivery system in providing substantial relief for RA. Furthermore, these findings support its effectiveness in inhibiting the disease process of RA, thereby offering new possibilities for the development of precise and accurate strategies for RA.


Assuntos
Artrite Reumatoide , Estruturas Metalorgânicas , Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Tirapazamina/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Hipóxia , Artrite Reumatoide/tratamento farmacológico , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico
16.
Food Chem ; 441: 138381, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38218150

RESUMO

The accumulation of the deoxynivalenol (DON) in the human body poses a significant health risk that is often overlooked, and we urgently need an ultra-sensitive rapid detection platform. Due to the porosity of NH2-MIL-101@MoS2, an increased loading of toluidine blue (TB) serves to create a signal reference. Cobalt@carbon (CoC) derived from metal organic frameworks was combined with NH2-MIL-101(NH2-MIL-101@CoC) to form an enzyme-free Nanoprobe (Apt-pro) with significant catalytic properties. The ratio (IBQ /ITB) was changed by varying the electrochemical signal of benzoquinone (BQ) (IBQ) and the amount of TB deposition (ITB). This aptasensor was successfully applied to detect DON in malt and peach seed, which exhibited a great linear range from 1 fg/mL to 10 ng/mL and low detection limit of 0.31 fg/mL for DON.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , Estruturas Metalorgânicas , Tricotecenos , Humanos , Estruturas Metalorgânicas/química , Peroxidase/química , Molibdênio , Corantes , Limite de Detecção , Técnicas Eletroquímicas , Aptâmeros de Nucleotídeos/química , Nanopartículas Metálicas/química
17.
Anal Chim Acta ; 1290: 342197, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38246739

RESUMO

BACKGROUND: Pretreatment techniques should be introduced before metal ion determination because there is very low content of heavy metals in Chinese medicinal plants and environmental samples. Magnetic dispersive micro solid phase extraction (MDMSPE) has been widely used for the separation and adsorption of heavy metal pollutants in medicinal plants and environmental samples. However, the majority of MDMSPE adsorbents have certain drawbacks, including low selectivity, poor anti-interference ability, and small adsorption capacity. Therefore, modifying currently available adsorption materials has gained attention in research. RESULTS: In this study, a novel adsorbent MCOF-DES based on a magnetic covalent organic framework (MCOF) modified by a new deep eutectic solvent (DES) was synthesized for the first time and used as an adsorbent of MDMSPE. The MDMSPE was combined with inductively coupled plasma optical emission spectrometry (ICP-OES) for selective separation, enrichment, and accurate determination of trace copper ion (Cu2+) in medicinal plants and environmental samples. Various characterization results show the successful preparation of new MCOF-DES. Under the optimal conditions, the enrichment factor (EF) of Cu2+ was 30, the limit of detection (LOD) was 0.16 µg L-1, and the limit of quantitation (LOQ) was 0.54 µg L-1. The results for the determination of Cu2+ were highly consistent with those of inductively coupled plasma mass spectrometry (ICP-MS), which verified the accuracy and reliability of the method. SIGNIFICANCE: The established method based on a new adsorption material MCOF-DES has achieved the selective separation and determination of trace Cu2+ in medicinal and edible homologous medicinal materials (Phyllanthus emblica Linn.) and environmental samples (soil and water), which provides a promising, selective, and sensitive approach for the determination of trace Cu2+ in other real samples.


Assuntos
Estruturas Metalorgânicas , Plantas Medicinais , Cobre , Solventes Eutéticos Profundos , Reprodutibilidade dos Testes , Fenômenos Magnéticos
18.
Environ Res ; 243: 117816, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38056614

RESUMO

Efficacious phosphate removal is essential for mitigating eutrophication in aquatic ecosystems and complying with increasingly stringent phosphate emission regulations. Chemical adsorption, characterized by simplicity, prominent treatment efficiency, and convenient recovery, is extensively employed for profound phosphorus removal. Metal-organic frameworks (MOFs)-derived metal/carbon composites, surpassing the limitations of separate components, exhibit synergistic effects, rendering them tremendously promising for environmental remediation. This comprehensive review systematically summarizes MOFs-based materials' properties and their structure-property relationships tailored for phosphate adsorption, thereby enhancing specificity towards phosphate. Furthermore, it elucidates the primary mechanisms influencing phosphate adsorption by MOFs-based composites. Additionally, the review introduces strategies for designing and synthesizing efficacious phosphorus capture and regeneration materials. Lastly, it discusses and illuminates future research challenges and prospects in this field. This summary provides novel insights for future research on superlative MOFs-based adsorbents for phosphate removal.


Assuntos
Estruturas Metalorgânicas , Fósforo , Água , Ecossistema , Fosfatos , Adsorção
19.
Int J Biol Macromol ; 254(Pt 3): 127702, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37956806

RESUMO

This study designed magnetic nanocomposite hydrogel beads for a potential targeted anticancer oral delivery system. To end this, nanohybrids of Fe3O4/MIL-88(Fe) (FM) were synthesized through in-situ method by the treatment of terephthalic acid (TPA) and (Fe(NO3)3·9H2O) in the presence of Fe3O4 nanoparticles. They were then modified with mannose sugar as an anticancer receptor to achieve a targeted drug delivery system. After loading methotrexate (MTX), they were coated with pH-sensitive pectin hydrogel beads in the presence of a calcium chloride crosslinker for possible transferring the nanohybrids to the intestine through the acidic environment of the digestive system. The results of different analysis techniques showed that the materials were properly synthesized, coated, and loaded. The designed magnetic nanocomposite hydrogel beads showed pH-sensitive swelling and drug release rate, protecting MTX from the acidic environment of the stomach. MTT test revealed a good cytotoxicity toward colon cancer HT29 cell lines. Remarkably, the functionalization of MTX-loaded FM nanohybrids with mannose (MTX-MFM) enhanced their anticancer properties up to about 20 %. The results recommended that the prepared novel magnetic nanocomposite hydrogel beads have a good potential to be used as a targeted anticancer oral delivery system.


Assuntos
Estruturas Metalorgânicas , Nanocompostos , Hidrogéis , Portadores de Fármacos , Manose , Nanogéis , Pectinas , Sistemas de Liberação de Medicamentos , Metotrexato , Fenômenos Magnéticos
20.
Acta Biomater ; 174: 372-385, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38072226

RESUMO

Targeted delivery of therapeutic drugs to fibrosis-promoting macrophages (FPMs) holds promise as a challenging yet effective approach for the treatment of idiopathic pulmonary fibrosis (IPF). Here, nanocarriers composed of Mn-curcumin metal-organic frameworks (MOFs) were utilized to deliver the immune inhibitor BLZ-945 to the lungs, with the goal of depleting fibrosis-promoting macrophages (FPMs) from fibrotic lung tissues. FPM targeting was achieved by functionalizing the nanocarrier surface with an M2-like FPM binding peptide (M2pep). As a result, significant therapeutic benefits were observed through the successful depletion of approximately 80 % of the M2-like macrophages (FPMs) in a bleomycin-induced fibrosis mouse model treated with the designed M2-like FPM-targeting nanoparticle (referred to as M2NP-BLZ@Mn-Cur). Importantly, the released Mn2+ and curcumin after the degradation of M2NP-BLZ@Mn-Cur accumulated in the fibrotic lung tissue, which can alleviate inflammation and oxidative stress reactions, thereby further improving IPF therapy. This study presents a novel strategy with promising prospects for molecular-targeted fibrosis therapy. STATEMENT OF SIGNIFICANCE: Metal-organic frameworks (MOFs)- based nanocarriers equipped with both fibrosis-promoting macrophage (FPM)-specific targeting ability and therapeutic drugs are appealing for pulmonary fibrosis treatment. Here, we prepared M2pep (an M2-like FPM binding peptide)-modified and BLZ945 (a small molecule inhibitor of CSF1/CSF-1R axis)-loaded Mn-curcumin MOF nanoparticles (M2NP-BLZ@Mn-Cur) for pulmonary fibrosis therapy. The functionalized M2NP-BLZ@Mn-Cur nanoparticles can be preferentially taken up by FPMs, resulting in their depletion from fibrotic lung tissues. In addition, Mn2+and curcumin released from the nanocarriers have anti-inflammation and immune regulation effects, which further enhance the antifibrotic effect of the nanoparticles.


Assuntos
Curcumina , Fibrose Pulmonar Idiopática , Estruturas Metalorgânicas , Camundongos , Animais , Estruturas Metalorgânicas/farmacologia , Curcumina/farmacologia , Curcumina/uso terapêutico , Curcumina/química , Macrófagos/metabolismo , Fibrose Pulmonar Idiopática/tratamento farmacológico , Fibrose Pulmonar Idiopática/metabolismo , Peptídeos/farmacologia
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