RESUMO
Metal-Organic Framework-199 (MOF-199) is a subgroup of MOFs that is utilized in different medical fields such as drug delivery. In the current study, the effect of sub-acute exposure to MOF-199 on spatial memory, working memory, inflammatory mediators' expression, and oxidative stress level of brain tissue has been investigated. Thirty-two male Wistar rats were randomly divided into four groups as vehicle, MOF-199 at doses 0.3, 3, or 6 mg/kg. After four injections of relevant interventions via tail vein during 14 days, behavioral parameters were investigated using Y-maze and Morris Water Maze (MWM) tests. Oxidative stress was measured by ferric reducing antioxidant power (FRAP) and thiobarbituric acid-reacting substance (TBARS) tests. The expression levels of TNF-α and IL-1ß were assessed by quantitative real-time reverse-transcription PCR (qRT-PCR). No significant differences were observed in working memory, spatial learning and memory of MOF-199 receiving rats. Additionally, the level of oxidative stress and inflammatory genes expression were not remarkably changed in the brain tissues of MOF-199 treated rats. Despite the lack of remarkable toxic effects of sub-acute exposure to MOF-199, more studies with a longer duration of administration are necessary to use this substance for drug delivery systems in diseases related to the nervous system.
Assuntos
Encéfalo , Cognição , Estruturas Metalorgânicas , Estresse Oxidativo , Ratos Wistar , Animais , Estresse Oxidativo/efeitos dos fármacos , Masculino , Encéfalo/metabolismo , Encéfalo/efeitos dos fármacos , Ratos , Cognição/efeitos dos fármacos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/toxicidade , Aprendizagem em Labirinto/efeitos dos fármacos , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/genética , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismoRESUMO
Herein, we developed a technique for loading nanopesticides onto Metal-Organic Frameworks (MOFs) to control Spodoptera litura. The average short-axis length of the synthesized carrier emamectin benzoate@PCN-222 @hyaluronic acid (EB@PCN-222 @HA) was â¼40 nm, with an average long-axis length of â¼80 nm. This enabled the manipulation of its size, contact angle, and surface tension on the surface of leaves. Pesticide-loading capacity, determined via thermogravimetric analysis, was measured at â¼16 %. To ensure accurate pesticide release in the alkaline intestine of Spodoptera litura, EB@PCN-222 @HA was engineered to decompose under alkaline conditions. In addition, the carrier delayed the degradation rate of EB, enhancing EB's stability. Loading Nile red onto PCN-222 @HA revealed potential entry into the insect body through feeding, which was supported by bioassay experiments. Results demonstrated the sustained-release performance of EB@PCN-222 @HA, extending its effective duration. The impact of different carrier concentrations on root length, stem length, fresh weight, and germination rate of pakchoi and tomato were assessed. Promisingly, the carrier exhibited a growth-promoting effect on the fresh weight of both the crops. Furthermore, cytotoxicity experiments confirmed its safety for humans. In cytotoxicity assays, PCN-222 @HA showed minimal toxicity at concentrations up to 100 mg/L, with cell survival rates above 80 %. Notably, the EB@PCN-222 @HA complex demonstrated reduced cytotoxicity compared to EB alone, supporting its safety for human applications. This study presents a safe and effective approach for pest control using controlled-release pesticides with extended effective durations.
Assuntos
Ivermectina , Estruturas Metalorgânicas , Spodoptera , Ivermectina/análogos & derivados , Ivermectina/toxicidade , Ivermectina/química , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/toxicidade , Animais , Concentração de Íons de Hidrogênio , Spodoptera/efeitos dos fármacos , Inseticidas/toxicidade , Inseticidas/química , Composição de Medicamentos , Ácido Hialurônico/química , Ácido Hialurônico/toxicidade , Solanum lycopersicumRESUMO
Over 9000 types of per- and polyfluoroalkyl substances (PFASs) have been produced that exhibit environmental persistence, bioaccumulation and biotoxicity, and pose a potential hazard to human health. Although metal-organic frameworks (MOFs) are promising structure-based materials for adsorbing PFASs, the enormous structural diversity and variability of the pharmacologic action of PFASs present challenges to the development of structure-based adsorbents. To address this issue, we propose an in situ platform for the high-throughput identification of efficient MOF sorbents that can adsorb PFASs and their metabolism using a filter-chip-solid phase extraction-mass spectrometry (SPE-MS) system. As a proof of concept, we screened BUT-16 as an attractive material for in situ fluorotelomer alcohol (FTOH) adsorption. The results demonstrated that FTOH molecules were adsorbed around the surface of the large hexagonal pores of BUT-16 by forming multiple hydrogen bonding interactions with its Zr6 clusters. The FTOH removal efficiency of the BUT16 filter was 100% over a period of 1 min. To determine the FTOH metabolism effects in different organs, HepG2 human hepatoma, HCT116 colon cancer, renal tubular HKC, and vascular endothelial HUVEC cells were cultured on a microfluidic chip, and SPE-MS was used to track a variety of cell metabolites in real time. Overall, the filter-Chip-SPE-MS system is a versatile and robust platform for the real-time monitoring of noxious pollutant detoxification, biotransformation, and metabolism, which facilitates pollutant antidote development and toxicology assay.
Assuntos
Poluentes Ambientais , Fluorocarbonos , Estruturas Metalorgânicas , Humanos , Estruturas Metalorgânicas/toxicidade , Microfluídica , Extração em Fase Sólida , Fluorocarbonos/toxicidade , Poluentes Ambientais/análiseRESUMO
The wide utilization of nano-sized metal-organic frameworks (NMOFs) leads to inevitable health risks to humans. Previous studies on health risks of NMOFs mainly focus on the cytotoxic tests of typical NMOFsï¼but lack sufficient studies on the effects of physiochemical characteristics of NMOFs on the cytotoxicity and the related mechanisms. Here, four kinds of Zr-based porphyrinic NMOFs (PCNs), including spherical 30, 90, and 180 nm PCN-224 and rod-like 90 nm PCN-222, were taken as a proof of the concept to investigate the effects of the size and shape of NMOFs on the cytotoxicity and related mechanisms to macrophages. The 30 nm spherical PCN-224 induced significant rupture of cell membrane and dissolved in lysosome, leading to the most significant cell necrosis among the studied other nano-sized PCNs. However, other studied PCNs showed insignificant membrane rupture and their dissolution in lysosome. Furthermore, the 90 nm-sized PCN-224 led to much more significant cell necrosis by inducing lysosome damage and inhibiting of autophagy flux than the rod-like 90 nm PCN-222. These findings reveal the size- and shape-dependent cytotoxicity of PCNs and the related mechanisms and are helpful to the assessment of the potential health risks of NMOFs and the safe application of NMOFs.
Assuntos
Antineoplásicos , Estruturas Metalorgânicas , Humanos , Macrófagos , Estruturas Metalorgânicas/toxicidade , NecroseRESUMO
In the last two decades, the field of metal-organic frameworks (MOFs) has exploded, and MOF nanoparticles in particular are being investigated with increasing interest for various applications, including gas storage and separation, water harvesting, catalysis, energy conversion and storage, sensing, diagnosis, therapy, and theranostics. To further pave their way into real-world applications, and to push the synthesis of MOF nanoparticles that are 'safe-and-sustainable-by-design', this tutorial review aims to shed light on the importance of a systematic toxicity assessment. After clarifying and working out the most important terms and aspects from the field of nanotoxicity, the current state-of-the-art of in vitro and in vivo toxicity studies of MOF nanoparticles is evaluated. Moreover, the key aspects affecting the toxicity of MOF nanoparticles such as their chemical composition, their physico-chemical properties, including their colloidal and chemical stability, are discussed. We highlight the need of more targeted synthesis of MOF nanoparticles that are 'safe-and-sustainable-by-design', and their tailored hazard assessment in the context of their potential applications in order to tap the full potential of this versatile material class in the future.
Assuntos
Estruturas Metalorgânicas , Nanopartículas , Catálise , Estruturas Metalorgânicas/toxicidade , Nanopartículas/toxicidadeRESUMO
Understanding the toxicity of metal-organic frameworks (MOFs) is important for improving their biocompatibility in further applications, especially the hematotoxicity of MOFs due to the unavoidable contact of MOFs with blood in biomedical science. Here we report the hematotoxicity and underlying mechanisms of nano-sized zeolite-like MOFs ZIF-8 and ZIF-67 because of their wide applications in biomedical science. ZIF-67 induced significant hemolysis of red blood cell (Rb) through breaking the structure of membrane due to the generation of free radicals, whereas ZIF-8 was hematocompatible. ZIF-67 was thus internalized by Rb and then bound with hemoglobin via hydrogen bond and van der Waals force, which influenced the structure and function of hemoglobin in accompany with heme release. These findings reveal the detailed mechanism of the hematological effects of MOFs on Rb and are helpful to the assessment of the toxicity and potential health risks of MOFs and the design of biosafe MOFs for biomedical applications.
Assuntos
Estruturas Metalorgânicas , Zeolitas , Eritrócitos , Hemoglobinas , Estruturas Metalorgânicas/toxicidade , Zeolitas/toxicidadeRESUMO
We demonstrate that the hierarchically porous metal hydroxide/metal-organic framework composite nanoarchitectures exhibit broad-spectrum removal activity for three chemically distinct toxic gases, viz. acid gases, base gases, and nitrogen oxides. A facile and general in-situ hydrolysis strategy combined with gentle ambient pressure drying (APD) was utilized to integrate both Zr(OH)4 and Ti(OH)4 with the amino-functionalized MOF-808 xerogel (G808-NH2). The M(OH)4/G808-NH2 xerogel composites manifested 3D crystalline porous networks and substantially hierarchical porosity, with controllable amounts of amorphous M(OH)4 nanoparticles residing at the edge of xerogel particles. Microbreakthrough tests were performed under both dry and moist conditions to evaluate the filtration capabilities of the composites against three representative compounds: SO2, NH3, and NO2. Compared with the pristine G808-NH2 xerogel, the incorporation of M(OH)4 effectively enhanced the broad-spectrum toxic chemical mitigation ability of the material, with the highest SO2, NH3, and NO2 breakthrough uptake reaching 74.5, 55.3, and 394.0 mg/g, respectively. Post-breakthrough characterization confirmed the abundant M-OH groups with diverse binding configurations, alongside the unsaturated M (IV) centers on the surface of M(OH)4 provided extra adsorption sites for irreversible toxic chemical capture besides Van der Waals driven physisorption. The ability to achieve high-capacity adsorption and strong retention for multiple contaminants is of great significance for real-world filtration applications.
Assuntos
Estruturas Metalorgânicas , Adsorção , Filtração , Hidróxidos/toxicidade , Estruturas Metalorgânicas/toxicidade , PorosidadeRESUMO
The excessive colonization of Propionibacterium acnes (P. acnes) is responsible for the genesis of acne vulgaris, a common inflammatory disease of skin. However, the conventional anti-acne therapies are always limited by various side effects, drug resistance, and poor skin permeability. Microneedles (MNs) are emerging topical drug delivery systems capable of noninvasively breaking through the skin stratum corneum barrier to efficiently enhance the transdermal drug penetration. Herein, MNs loaded with intelligent pH-sensitive nanoplatforms were constructed for amplified chemo-photodynamic therapy against acne vulgaris, jointly exerting antimicrobial and anti-inflammatory effects. The photosensitizer indocyanine green (ICG) was loaded into the zeolitic imidazolate framework-8 (ZIF-8) to improve its photostability, which would be triggered by 808 nm laser irradiation to generate cytotoxic reactive oxygen species (ROS) to result in oxidative damage and disturbed metabolic activities of P. acnes. In addition to the efficient drug delivery, the ZIF-8 carrier could selectively degrade in response to the acidic microenvironment of acne lesions, and the released Zn2+ also exhibited a potent antimicrobial activity. The fabricated ZIF-8-ICG@MNs presented an outstanding synergistic anti-acne efficiency both in vitro and in vivo. This bioresponsive microneedle patch is expected to be readily adapted as a generalized, modular strategy for noninvasive therapeutics delivery against superficial skin diseases.
Assuntos
Acne Vulgar/tratamento farmacológico , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Imidazóis/uso terapêutico , Verde de Indocianina/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Acne Vulgar/patologia , Animais , Antibacterianos/química , Antibacterianos/efeitos da radiação , Antibacterianos/toxicidade , Anti-Inflamatórios/química , Anti-Inflamatórios/efeitos da radiação , Anti-Inflamatórios/toxicidade , Células HEK293 , Humanos , Imidazóis/química , Imidazóis/efeitos da radiação , Imidazóis/toxicidade , Verde de Indocianina/química , Verde de Indocianina/efeitos da radiação , Verde de Indocianina/toxicidade , Raios Infravermelhos , Masculino , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/efeitos da radiação , Estruturas Metalorgânicas/toxicidade , Camundongos Endogâmicos BALB C , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Propionibacterium acnes/efeitos dos fármacos , Ratos , Pele/efeitos dos fármacos , Pele/patologia , Suínos , Zinco/química , Zinco/efeitos da radiação , Zinco/uso terapêutico , Zinco/toxicidadeRESUMO
Black phosphorus (BP) nanosheet is easily oxidized by oxygen and water under ambient environment, thus, reliable BP passivation techniques for biomedical applications is urgently needed. A simple and applicable passivation strategy for biomedical applications was established by encapsulating BP nanosheet into zeolitic imidazole framework-8 (ZIF-8). The resulted BP nanosheet in ZIF-8 (BP@ZIF-8) shows not only satisfied chemical stability in both water and phosphate buffered saline (PBS), but also excellent biocompatibility. Notably, BP nanosheet endows the prepared BP@ZIF-8 with prominent photothermal conversion efficiency (31.90%). Besides passivation BP, ZIF-8 provides the BP@ZIF-8 with high drug loading amount (1353.3 mg g-1). Moreover, the loaded drug can be controlled release by pH stimuli. Both in vitro and in vivo researches verified the resulted BP@ZIF-8 an ideal candidate for tumor multimodal treatments.
Assuntos
Antineoplásicos/uso terapêutico , Portadores de Fármacos/química , Estruturas Metalorgânicas/química , Nanoestruturas/química , Neoplasias/tratamento farmacológico , Fósforo/química , Animais , Antineoplásicos/química , Linhagem Celular Tumoral , Terapia Combinada , Doxorrubicina/química , Doxorrubicina/uso terapêutico , Portadores de Fármacos/efeitos da radiação , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Tratamento Farmacológico , Feminino , Humanos , Concentração de Íons de Hidrogênio , Raios Infravermelhos , Estruturas Metalorgânicas/efeitos da radiação , Estruturas Metalorgânicas/toxicidade , Camundongos , Nanoestruturas/efeitos da radiação , Nanoestruturas/toxicidade , Fósforo/efeitos da radiação , Fósforo/toxicidade , Terapia FototérmicaRESUMO
Overproduction of reactive oxygen species (ROS) within tumors can cause oxidative stress on tumor cells to induce death, which has motivated us to develop ROS-mediated tumor therapies, such as typical photodynamic therapy (PDT) and Fenton reaction-mediated chemodynamic therapy (CDT). However, these therapeutic modalities suffer from compromised treatment efficacy owing to their limited generation of highly reactive ROS in a tumor microenvironment (TME). In this work, a nanoscale iron-based metal-organic framework, MIL-101(Fe), is synthesized as a Fenton nanocatalyst to perform the catalytic conversion of hydroxyl radicals (·OH) from hydrogen peroxide (H2O2) under the acidic environment and as a biocompatible and biodegradable nanocarrier to deliver a 5,10,15,20-tetrakis(4-carboxyphenyl)porphyrin (TCPP) photosensitizer for light-activated singlet oxygen (1O2) generation. By coupling such chemodynamic/photodynamic effects, the photosensitizer-integrated nanoagents (MIL-101(Fe)@TCPP) could enable more ROS production within tumors to induce amplified oxidative damage for tumor-specific synergistic therapy. In vitro results show that MIL-101(Fe)@TCPP nanoagents achieve the acid-responsive CDT and effective PDT, and synergistic CDT/PDT provides an enhanced therapeutic effect. Ultimately, based on such synergistic therapy, MIL-101(Fe)@TCPP nanoagents cause a significant tumor growth inhibition in vivo without severe side effects, showing great potential for anti-tumor application.
Assuntos
Antineoplásicos/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Nanoestruturas/uso terapêutico , Neoplasias/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fármacos Fotossensibilizantes/uso terapêutico , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/toxicidade , Catálise , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Peróxido de Hidrogênio/química , Radical Hidroxila/metabolismo , Ferro/química , Luz , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Estruturas Metalorgânicas/toxicidade , Nanoestruturas/química , Nanoestruturas/toxicidade , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Porfirinas/farmacologia , Porfirinas/efeitos da radiação , Porfirinas/uso terapêutico , Porfirinas/toxicidade , Oxigênio Singlete/metabolismoRESUMO
Fabrication of porous materials with a high surface area affords a great interest to achieve a system with a prolonged drug release manner. In this context, the subject of this work is to describe a novel green one-pot synthesis route for the growth of metal-organic framework (MOF) from zinc metal (Zn) and 1, 4-benzene dicarboxylic acid (BDC) in the vicinity of the carboxymethyl cellulose (CMC), which homogeneously confined in the biopolymeric chains. The synthesized Zn (BDC)@CMC was characterized and confirmed using different analyses. N2 adsorption/desorption isotherms determined the mean diameter of pore size of about 2.3993 nm. Ibuprofen (IBU) as a model drug was highly loaded to the Zn(BDC)@CMC by immersing in the drug solution; 50.95%. The in vitro IBU release study indicated that the Zn(BDC)@CMC has more attractive performances than pristine Zn(BDC). The IBU release occurred via the Fickian mechanism. Isotherm studies showed that the IBU adsorption on obeys from Langmuir isotherm; R2 0.9623. The MTT results revealed the HEK 293A cell viability of higher than 90% for Zn(BDC)@CMC that confirms its cytocompatibility. Overall, obtained results confirm the functionality of CMC biopolymer for in situ growth of MOF in the presence of it due to having the reactive nature.
Assuntos
Carboximetilcelulose Sódica/química , Portadores de Fármacos/síntese química , Estruturas Metalorgânicas/síntese química , Zinco/química , Anti-Inflamatórios não Esteroides/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/toxicidade , Células HEK293 , Humanos , Ibuprofeno/administração & dosagem , Estruturas Metalorgânicas/toxicidadeRESUMO
Metal-organic frameworks (MOFs) are an emerging class of materials which have garnered increasing attention for their utility as adsorbents and photocatalysts in water treatment. Nevertheless, the environmental risks of MOFs, especially their underlying impacts on aquatic organisms, are not fully explored. Herein, the toxicity of multiple representative MOFs was systematically assessed using a freshwater green alga (Chlamydomonas reinhardtii) model. Six typical MOFs with different metal nodes or organic linkers, including four transition metal incorporated aluminum-based porphyrin MOFs [pristine Al-PMOF, Al-PMOF (Cu), Al-PMOF (Ni), and Al-PMOF (Co)], one amine-functionalized MOF NH2-MIL-125 (Ti), and one bimetallic Hofmann MOF (NiCo-PYZ), were successfully synthesized and characterized. All the tested MOFs significantly reduced the chlorophyll content and inhibited the algal growth, with the most toxic materials being NiCo-PYZ and Al-PMOF (Cu). Distinct toxic mechanisms were observed for the tested MOFs. Metal ion release was the primary cause for algal toxicity induced by NiCo-PYZ. The algal toxicity induced by porphyrin MOFs could be explained by the combined effects of metal ion release and nutrient adsorption, agglomeration and physical interactions, and reactive oxygen species generation. NH2-MIL-125 (Ti) showed higher stability and more biocompatibility than the other tested MOFs. MOFs concentrations with no harmful effects to algae can be taken as the threshold values for safe use and discharge of MOFs. The ecotoxicological risks of MOFs should be considered as the applied concentrations of MOFs at mg/mL levels in environmental remediation were much higher than the no harmful effect thresholds.
Assuntos
Chlamydomonas reinhardtii , Estruturas Metalorgânicas , Porfirinas , Purificação da Água , Adsorção , Estruturas Metalorgânicas/toxicidadeRESUMO
Chronic wound healing, impeded by bacterial infections and drug resistance, poses a threat to global human health. Antibacterial phototherapy is an effective way to fight microbial infection without causing drug resistance. Covalent organic frameworks (COFs) are a class of highly crystalline functional porous carbon-based materials composed of light atoms (e.g., carbon, nitrogen, oxygen, and borane), showing potential applications in the biomedical field. Herein, we constructed porphyrin-based COF nanosheets (TP-Por CON) for synergizing photodynamic and photothermal therapy under red light irradiation (e.g., 635 nm). Moreover, a nitric oxide (NO) donor molecule, BNN6, was encapsulated into the pore volume of the crystalline porous framework structure to moderately release NO triggered by red light irradiation for realizing gaseous therapy. Therefore, we successfully synthesized a novel TP-Por CON@BNN6-integrated heterojunction for thoroughly killing Gram-negative bacteria Escherichia coli and Gram-positive bacteria Staphylococcus aureus in vitro. Our research identified that TP-Por CON@BNN6 has favorable biocompatibility and biodegradability, low phototoxicity, anti-inflammatory properties, and excellent mice wound healing ability in vivo. This study indicates that the TP-Por CON@BNN6-integrated heterojunction with multifunctional properties provides a potential strategy for COF-based gaseous therapy and microorganism-infected chronic wound healing.
Assuntos
Anti-Inflamatórios/uso terapêutico , Estruturas Metalorgânicas/uso terapêutico , Doadores de Óxido Nítrico/uso terapêutico , Fármacos Fotossensibilizantes/uso terapêutico , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Cicatrização/efeitos dos fármacos , Animais , Anti-Inflamatórios/efeitos da radiação , Anti-Inflamatórios/toxicidade , Linhagem Celular , Escherichia coli/efeitos dos fármacos , Luz , Estruturas Metalorgânicas/efeitos da radiação , Estruturas Metalorgânicas/toxicidade , Camundongos Endogâmicos BALB C , Doadores de Óxido Nítrico/efeitos da radiação , Doadores de Óxido Nítrico/toxicidade , Fármacos Fotossensibilizantes/efeitos da radiação , Fármacos Fotossensibilizantes/toxicidade , Porfirinas/efeitos da radiação , Porfirinas/uso terapêutico , Porfirinas/toxicidade , Staphylococcus aureus/efeitos dos fármacosRESUMO
The removal of uremic toxins from patients with acute kidney injury is a key issue in improving the quality of life for people requiring peritoneal dialysis. The currently utilized method for the removal of uremic toxins from the human organism is hemodialysis, performed on semipermeable membranes where the uremic toxins, along with small molecules, are separated from proteins and blood cells. In this study, we describe a mixed-linker modulated synthesis of zirconium-based metal-organic frameworks for efficient removal of uremic toxins. We determined that the efficient adsorption of uremic toxins is achieved by optimizing the ratio between -amino functionalization of the UiO-66 structure with 75% of -NH2 groups within organic linker structure. The maximum adsorption of hippuric acid and 3-indoloacetic acid was achieved by UiO-66-NH2 (75%) and by UiO-66-NH2 (75%) 12.5% HCl prepared by modulated synthesis. Furthermore, UiO-66-NH2 (75%) almost completely adsorbs 3-indoloacetic acid bound to bovine serum albumin, which was used as a model protein to which uremic toxins bind in the human body. The high adsorption capacity was confirmed in recyclability test, which showed almost 80% removal of 3-indoloacetic acid after the third adsorption cycle. Furthermore, in vitro cytotoxicity tests as well as hemolytic activity assay have proven that the UiO-66-based materials can be considered as potentially safe for hemodialytic purposes in living organisms.
Assuntos
Hipuratos/isolamento & purificação , Ácidos Indolacéticos/isolamento & purificação , Rins Artificiais , Estruturas Metalorgânicas/química , Ácidos Ftálicos/química , Toxinas Urêmicas/isolamento & purificação , Adsorção , Animais , Chlorocebus aethiops , Eritrócitos/efeitos dos fármacos , Células HEK293 , Hipuratos/química , Humanos , Ácidos Indolacéticos/química , Estruturas Metalorgânicas/síntese química , Estruturas Metalorgânicas/toxicidade , Ácidos Ftálicos/síntese química , Ácidos Ftálicos/toxicidade , Toxinas Urêmicas/química , Células Vero , Zircônio/químicaRESUMO
Covalent organic frameworks (COFs) have emerged as promising materials for biomedical applications, but their functions remain to be explored and the potential toxicity concerns should be resolved. Herein, it is presented that carbonization significantly enhances the fluorescence quenching efficiency and aqueous stability of nanoscale COFs. The probes prepared by physisorbing dye-labeled nucleic acid recognition sequences onto the carbonized COF nanoparticles (termed C-COF) were employed for cell imaging, which could effectively light up biomarkers (survivin and TK1 mRNA) in living cells. The C-COF has enhanced photothermal conversion capacity, indicating that the probes are also promising candidates for photothermal therapy. The potential toxicity concern from the aromatic rigid building units of COFs was detoured by carbonization. Overall, carbonization is a promising strategy for developing biocompatible and multifunctional COF-derived nanoprobes for biomedical applications. This work may inspire more versatile COF-derived nanoprobes for bioanalysis and nanomedicine.
Assuntos
Biomarcadores Tumorais/análise , DNA/química , Corantes Fluorescentes/química , Estruturas Metalorgânicas/química , Nanopartículas/química , RNA Mensageiro/análise , Biomarcadores Tumorais/genética , Carbono/química , Carbono/toxicidade , Linhagem Celular Tumoral , DNA/toxicidade , Corantes Fluorescentes/toxicidade , Humanos , Ácidos Nucleicos Imobilizados/química , Ácidos Nucleicos Imobilizados/toxicidade , Estruturas Metalorgânicas/toxicidade , Microscopia Confocal , Microscopia de Fluorescência , Nanopartículas/toxicidade , Neoplasias/diagnóstico por imagem , RNA Mensageiro/genética , Survivina/genética , Timidina Quinase/genéticaRESUMO
Polymer nanocapsules, with a hollow structure, are increasingly finding widespread use as drug delivery carriers; however, quantitatively evaluating the bio-nano interactions of nanocapsules remains challenging. Herein, poly(ethylene glycol) (PEG)-based metal-phenolic network (MPN) nanocapsules of three sizes (50, 100, and 150 nm) are engineered via supramolecular template-assisted assembly and the effect of the nanocapsule size on bio-nano interactions is investigated using in vitro cell experiments, ex vivo whole blood assays, and in vivo rat models. To track the nanocapsules by mass cytometry, a preformed gold nanoparticle (14 nm) is encapsulated into each PEG-MPN nanocapsule. The results reveal that decreasing the size of the PEG-MPN nanocapsules from 150 to 50 nm leads to reduced association (up to 70%) with phagocytic blood cells in human blood and prolongs in vivo systemic exposure in rat models. The findings provide insights into MPN-based nanocapsules and represent a platform for studying bio-nano interactions.
Assuntos
Sangue/metabolismo , Estruturas Metalorgânicas/química , Nanocápsulas/química , Polietilenoglicóis/química , Pirogalol/análogos & derivados , Animais , Citometria de Fluxo/métodos , Ouro/química , Ouro/metabolismo , Ouro/farmacocinética , Ouro/toxicidade , Humanos , Masculino , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Estruturas Metalorgânicas/metabolismo , Estruturas Metalorgânicas/farmacocinética , Estruturas Metalorgânicas/toxicidade , Camundongos , Nanocápsulas/toxicidade , Tamanho da Partícula , Polietilenoglicóis/metabolismo , Polietilenoglicóis/farmacocinética , Polietilenoglicóis/toxicidade , Pirogalol/metabolismo , Pirogalol/farmacocinética , Pirogalol/toxicidade , Células RAW 264.7 , Ratos Sprague-DawleyRESUMO
Metal-organic frameworks (MOFs) exhibit broad potential applications in the environmental, biomedical, catalyst, and energy fields. However, the currently existing data hardly shed light on their health risks before the MOFs' large-scale usage. In this context, we exploratively investigated the in vivo fate and effect of one representative cobalt-based zeolitic imidazolate framework (ZIF-67) at the nano- (60 nm) and submicron- (890 nm) scales. Different from submicron-scale ZIF-67 showing better biosafety, nanoscale particles manifested a neurodegenerative risk at the dose of no general toxicity, evidenced by the impairment of learning and memory ability and disordered function of the neuropeptide signaling pathway in a rat model. The involvement of oxidative damage and inflammatory processes in the neurotoxicity induced by ZIF-67 was discussed as well. These findings not only provide a wake-up call for the prudent applications of MOFs but also provide insight into the better design and safer use of MOFs for broader applications.
Assuntos
Estruturas Metalorgânicas , Zeolitas , Animais , Catálise , Cobalto/toxicidade , Estruturas Metalorgânicas/toxicidade , Ratos , Zeolitas/toxicidadeRESUMO
Herein, the NH2-UiO-66 metal organic framework (MOF) has been green synthesized with the assistance of high gravity to provide a suitable and safe platform for drug loading. The NH2-UiO-66 MOF was characterized using a field-emission scanning electron microscope, transmission electron microscope (TEM), X-ray diffraction, and zeta potential analysis. Doxorubicin was then encapsulated physically on the porosity of the green MOF. Two different stimulus polymers, p(HEMA) and p(NIPAM), were used as the coating agents of the MOFs. Doxorubicin was loaded onto the polymer-coated MOFs as well, and a drug payload of more than 51% was obtained, which is a record by itself. In the next step, pCRISPR was successfully tagged on the surface of the modified MOFs, and the performance of the final nanosystems were evaluated by the GFP expression. In addition, successful loadings and internalizations of doxorubicin were investigated via confocal laser scanning microscopy. Cellular images from the HeLa cell line for the UiO-66@DOX@pCRISPR and GMA-UiO-66@DOX@pCRISPR do not show any promising and successful gene transfections, with a maximum EGFP of 1.6%; however, the results for the p(HEMA)-GMA-UiO-66@DOX@pCRISPR show up to 4.3% transfection efficiency. Also, the results for the p(NIPAM)-GMA-UiO-66@DOX@pCRISPR showed up to 6.4% transfection efficiency, which is the first and superior report of a MOF-based nanocarrier for the delivery of pCRISPR. Furthermore, the MTT assay does not shown any critical cytotoxicity, which is a promising result for further biomedical applications. At the end of the study, the morphologies of all of the nanomaterials were screened after drug and gene delivery procedures and showed partial degradation of the nanomaterial. However, the cubic structure of the MOFs has been shown in TEM, and this is further proof of the stability of these green MOFs for biomedical applications.
Assuntos
Resinas Acrílicas/química , Sistemas CRISPR-Cas , Doxorrubicina/metabolismo , Portadores de Fármacos/química , Estruturas Metalorgânicas/química , Poli-Hidroxietil Metacrilato/química , Resinas Acrílicas/toxicidade , Adsorção , Doxorrubicina/química , Portadores de Fármacos/toxicidade , Liberação Controlada de Fármacos , Técnicas de Transferência de Genes , Química Verde , Proteínas de Fluorescência Verde/genética , Células HEK293 , Células HeLa , Humanos , Estruturas Metalorgânicas/toxicidade , Poli-Hidroxietil Metacrilato/toxicidade , PorosidadeRESUMO
The structural modulation of multicompartment porous nanomaterials is one of the major challenges of nanoscience. Herein, by utilizing the polyhedral effects/characteristics of metal-organic frameworks (MOFs), we present a versatile approach to construct MOF-organosilica hybrid branched nanocomposites with MOF cores, SiO2 shells, and periodic mesoporous organosilica (PMO) branches. The morphology, structure, and functions of the obtained hybrid nanocomposites can be facilely modulated by varying particle size, shape, or crystalline structures of the MOF cores. Specifically, these branched multicompartment porous nanoparticles exhibit evasion behaviors in epithelial cells compared with macrophage cells, which may endow them great potential as a vehicle for immunotherapy.
Assuntos
Estruturas Metalorgânicas/síntese química , Nanocompostos/química , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Humanos , Macrófagos/efeitos dos fármacos , Estruturas Metalorgânicas/toxicidade , Camundongos , Nanocompostos/toxicidade , Tamanho da Partícula , Porosidade , Células RAW 264.7 , Dióxido de Silício/química , Dióxido de Silício/toxicidadeRESUMO
Metal-organic frameworks (MOFs) are innovative porous structures consisting of metal ions and organic ligands, which have been verified for extraordinary applications in nanomedicine and pharmaceuticals. PCN-224 is a type of Zr-based MOFs, which has recently emerged as one of the most attractive nanomaterials for various applications, such as drug delivery, bioimaging and cancer therapy due to its favorable and fascinating physical-chemical properties. However, the safety evaluation and the potential toxicological properties remain unclear. In this study, the general cytotoxicity of PCN-224 were examined in both human hepatocytes L-02 cells and mouse macrophages RAW264.7. Furthermore, the effect of inflammation and autophagy were measured in L-02 cells. The results indicated that PCN-224 was engulfed in L-02 cells and subsequently resulted in morphological changes, cell membrane destruction, and oxidative stress in L-02 cells. PCN-224 might trigger inflammation by promoting the secretion of inflammatory factors such as Tumor necrosis factors (TNF-α) and Interleukin (IL-6). PCN-224 might induce autophagosome accumulation and subsequently autophagic dysfunction. Additionally, PCN-224 induced cytotoxicity in RAW264.7 cells and increased the protein levels of the inflammasome component NLR Family Pyrin Domain Containing 3 (NLRP3) molecular, which indicated its cellular effects in different cell types. All of these results will support the reasonable use of PCN-224.