RESUMO
Microbial blooms have been reported in the First Generation Magnox Storage Pond at the Sellafield Nuclear Facility. The pond is kept alkaline with NaOH to minimise fuel rod corrosion, however alkali-tolerant microbial blooms dominated by the cyanobacterium Pseudanabaena catenata are able to thrive in this hostile environment. This study assessed the impact of alternative alkali-dosing regimens (KOH versus NaOH treatment) on biomass accumulation, using a P. catenata dominated mixed culture, which is representative of the pond environment. Optical density was reduced by 40-67 % with KOH treatment over the 3-month chemostat experiment. Microbial community analysis and proteomics demonstrated that the KOH-dependent inhibition of cell growth was mostly specific to P. catenata. The addition of KOH to nuclear storage ponds may therefore help control growth of this pioneer photosynthetic organism due to its sensitivity to potassium, while maintaining the high pH needed to inhibit the corrosion of stored nuclear fuel.
Assuntos
Cianobactérias , Lagoas , Cianobactérias/crescimento & desenvolvimento , Cianobactérias/metabolismo , Cianobactérias/fisiologia , Lagoas/microbiologia , Compostos de Potássio/farmacologia , Hidróxidos/farmacologia , Potássio/metabolismo , Potássio/análise , BiomassaRESUMO
The development of nanoformulations with simple compositions that can exert targeted combination therapy still remains a great challenge in the area of precision cancer nanomedicine. Herein, we report the design of a multifunctional nanoplatform based on methotrexate (MTX)-loaded layered double hydroxide (LDH) coated with chlorin e6 (Ce6)-modified MCF-7 cell membranes (CMM) for combined chemo/sonodynamic therapy of breast cancer. LDH nanoparticles were in situ loaded with MTX via coprecipitation, and coated with CMM that were finally functionalized with phospholipid-modified Ce6. The created nanoformulation of LDH-MTX@CMM-Ce6 displays good colloidal stability under physiological conditions and can release MTX in a pH-dependent manner. We show that the formulation can homologously target breast cancer cells, and induce their significant apoptosis through arresting the cell cycle via cooperative MTX-based chemotherapy and ultrasound (US)-activated sonodynamic therapy. The assistance of US can not only trigger sonosensitizer Ce6 to produce reactive oxygen species, but also enhance the cellular uptake of LDH-MTX@CMM-Ce6 via an acoustic cavitation effect. Upon intravenous injection and US irradiation, LDH-MTX@CMM-Ce6 displays an admirable antitumor performance towards a xenografted breast tumor mouse model. Furthermore, the modification of Ce6 on the CMM endows the LDH-based nanoplatform with fluorescence imaging capability. The developed LDH-based nanoformulation here provides a general intelligent cancer nanomedicine platform with simple composition and homologous targeting specificity for combined chemo/sonodynamic therapy and fluorescence imaging of tumors.
Assuntos
Clorofilídeos , Hidróxidos , Metotrexato , Nanopartículas , Porfirinas , Terapia por Ultrassom , Humanos , Animais , Metotrexato/química , Metotrexato/farmacologia , Hidróxidos/química , Hidróxidos/farmacologia , Camundongos , Feminino , Porfirinas/química , Porfirinas/farmacologia , Nanopartículas/química , Células MCF-7 , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Membrana Celular/química , Membrana Celular/metabolismo , Camundongos Endogâmicos BALB C , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Camundongos Nus , Proliferação de Células/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Tamanho da Partícula , Ensaios de Seleção de Medicamentos Antitumorais , Propriedades de SuperfícieRESUMO
Nickel-titanium alloy stents are widely used in the interventional treatment of various malignant tumors, and it is important to develop nickel-titanium alloy stents with selective cancer-inhibiting and antibacterial functions to avoid malignant obstruction caused by tumor invasion and bacterial colonization. In this work, an acid-responsive layered double hydroxide (LDH) film was constructed on the surface of a nickel-titanium alloy by hydrothermal treatment. The release of nickel ions from the film in the acidic tumor microenvironment induces an intracellular oxidative stress response that leads to cell death. In addition, the specific surface area of LDH nanosheets could be further regulated by heat treatment to modulate the release of nickel ions in the acidic microenvironment, allowing the antitumor effect to be further enhanced. This acid-responsive LDH film also shows a good antibacterial effect against S. aureus and E. coli. Besides, the LDH film prepared without the introduction of additional elements maintains low toxicity to normal cells in a normal physiological environment. This work offers some guidance for the design of a practical nickel-titanium alloy stent for the interventional treatment of tumors.
Assuntos
Antibacterianos , Hidróxidos , Níquel , Microambiente Tumoral , Hidróxidos/química , Hidróxidos/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Níquel/química , Níquel/farmacologia , Humanos , Antibacterianos/farmacologia , Antibacterianos/química , Ligas/química , Ligas/farmacologia , Escherichia coli/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Titânio/química , Titânio/farmacologia , Antineoplásicos/farmacologia , Antineoplásicos/química , Concentração de Íons de HidrogênioRESUMO
Sonodynamic therapy (SDT), a promising strategy for cancer treatment with the ability for deep tissue penetration, has received widespread attention in recent years. Sonosensitizers with intrinsic characteristics for tumor-specific curative effects, tumor microenvironment (TME) regulation and tumor diagnosis are in high demand. Herein, amorphous CoBiMn-layered double hydroxide (a-CoBiMn-LDH) nanoparticles are presented as multifunctional sonosensitizers to trigger reactive oxygen species (ROS) generation for ultrasound (US) imaging-guided SDT. Hydrothermal-synthesized CoBiMn-LDH nanoparticles are etched via a simple acid treatment to obtain a-CoBiMn-LDH nanoparticles with abundant defects. The a-CoBiMn-LDH nanoparticles give greater ROS generation upon US irradiation, reaching levels ~ 3.3 times and ~ 8.2 times those of the crystalline CoBiMn-LDH nanoparticles and commercial TiO2 sonosensitizer, respectively. This excellent US-triggered ROS generation performance can be attributed to the defect-induced narrow band gap and promoted electrons and holes (e-/h+) separation. More importantly, the presence of Mn4+ enables the a-CoBiMn-LDH nanoparticles to regulate the TME by decomposing H2O2 into O2 for hypoxia relief and US imaging, and consuming glutathione (GSH) for protection against ROS clearance. Biological mechanism analysis shows that a-CoBiMn-LDH nanoparticles modified with polyethylene glycol can serve as a multifunctional sonosensitizer to effectively kill cancer cells in vitro and eliminate tumors in vivo under US irradiation by activating p53, apoptosis, and oxidative phosphorylation-related signaling pathways.
Assuntos
Hidróxidos , Nanopartículas , Espécies Reativas de Oxigênio , Microambiente Tumoral , Terapia por Ultrassom , Microambiente Tumoral/efeitos dos fármacos , Animais , Espécies Reativas de Oxigênio/metabolismo , Humanos , Terapia por Ultrassom/métodos , Hidróxidos/química , Hidróxidos/farmacologia , Camundongos , Nanopartículas/química , Linhagem Celular Tumoral , Cobalto/química , Ultrassonografia/métodos , Camundongos Endogâmicos BALB C , Neoplasias/terapia , Neoplasias/diagnóstico por imagem , Apoptose/efeitos dos fármacos , Feminino , Camundongos NusRESUMO
Critical limb ischemia (CLI) refers to a severe condition resulting from gradual obstruction in the supply of blood, oxygen, and nutrients to the limbs. The most promising clinical solution to CLI is therapeutic angiogenesis. This study explored the potency of pro-angiogenic terbium hydroxide nanorods (THNR) for treatment of CLI, with a major focus on their impact on ischemia-induced maladaptive alterations in endothelial cells as well as on vascularization in ischemic limbs. This study demonstrated that, in hypoxia-exposed endothelial cells, THNR improve survival and promote proliferation, migration, restoration of nitric oxide production, and regulation of vascular permeability. Based on molecular studies, these attributes of THNR can be traced to the stimulation of PI3K/AKT/eNOS signaling pathways. Besides, Wnt/GSK-3ß/ß-catenin signaling pathways may also play a role in the therapeutic actions of THNR. Furthermore, in the murine model of CLI, THNR administration can integrally re-establish blood perfusion with concomitant reduction of muscle damage and inflammation. Additionally, improvement of locomotor activities and motor coordination in ischemic limbs in THNR treated mice is also evident. Overall, the study demonstrates that THNR have the potential to be developed as an efficacious and cost-effective alternative clinical therapy for CLI, using a nanomedicine approach.
Assuntos
Isquemia , Nanotubos , Animais , Nanotubos/química , Camundongos , Isquemia/tratamento farmacológico , Isquemia/patologia , Isquemia/metabolismo , Humanos , Hidróxidos/química , Hidróxidos/farmacologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Masculino , Teste de Materiais , Proliferação de Células/efeitos dos fármacos , Tamanho da Partícula , Camundongos Endogâmicos C57BL , Células Endoteliais da Veia Umbilical Humana , Membro Posterior/patologiaRESUMO
Minimally invasive embolization greatly decreases the mortality resulting from vascular injuries while still suffering from a high risk of recanalization and systematic thrombosis due to the intrinsic hydrophobicity and poor adhesion of the clinically used liquid embolic agent of Lipiodol. In this study, a shape self-adaptive liquid embolic agent was developed by mixing biocompatible poly(acrylic acid) (PAA), two-dimensional magnesium-aluminum layered double hydroxide (LDH), and poly(ethylene glycol)200 (PEG200). Upon contact with blood, the injectable PAA-LDH@PEG200 would quickly absorb water to form an adhesive and mechanically strong PAA-LDH thin hydrogel within 5 s, which could firmly adhere to the blood vessel wall for ultrafast and durable embolization. In addition, benefiting from the "positively charged nucleic center effect" of LDH nanosheets, the liquid PAA-LDH@PEG200 could avoid vascular distension by PAA overexpansion and possess high shock-resistant mechanical strength from the blood flow. Furthermore, both in vitro and in vivo embolization experiments demonstrated the complete embolic capacity of liquid PAA-LDH@PEG200 without the occurrence of recanalization for 28 days and also the great potential to act as a platform to couple with chemotherapeutic drugs for the minimized transcatheter arterial chemoembolization (TACE) treatment of VX2 tumors without recurrence for 18 days. Thus, liquid PAA-LDH@PEG200 developed here possesses great potential to act as a shape self-adaptive liquid embolic agent for ultrafast and durable vascular embolization.
Assuntos
Polietilenoglicóis , Animais , Polietilenoglicóis/química , Camundongos , Resinas Acrílicas/química , Embolização Terapêutica/métodos , Humanos , Hidróxidos/química , Hidróxidos/farmacologia , Hidrogéis/química , Hidrogéis/farmacologia , Alumínio/químicaRESUMO
As the main challenge of dental healthcare, oral infectious diseases are highly associated with the colonization of pathogenic microbes. However, current antibacterial treatments in the field of stomatology still lack a facile, safe, and universal approach. Herein, we report the controllable synthesis of copper aluminum-layered double hydroxides (CuAl-LDHs) with high Fenton-like catalytic activity, which can be utilized in the treatment of oral infectious diseases with negligible side effects. Our strategy can efficiently avoid the unwanted doping of other divalent metal ions in the synthesis of Cu-contained LDHs and result in the formation of binary CuAl-LDHs with high crystallinity and purity. Evidenced by experimental and theoretical results, CuAl-LDHs exhibit excellent catalytic ability toward the ·OH generation in the presence of H2O2 and hold strong affinity toward bacteria, endowing them with great catalytic sterilization against both Gram-positive and Gram-negative bacteria. As expected, these CuAl-LDHs provide outstanding treatments for mucosal infection and periodontitis by promoting wound healing and remodeling of the periodontal microenvironment. Moreover, toxicity investigation demonstrates the overall safety. Accordingly, the current study not only provides a convenient and economic strategy for treating oral infectious diseases but also extends the development of novel LDH-based Fenton or Fenton-like antibacterial reagents for further biomedical applications.
Assuntos
Alumínio , Antibacterianos , Cobre , Peróxido de Hidrogênio , Cobre/química , Cobre/farmacologia , Catálise , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/farmacologia , Alumínio/química , Alumínio/farmacologia , Hidróxidos/química , Hidróxidos/farmacologia , Testes de Sensibilidade Microbiana , Animais , Ferro/química , Ferro/farmacologia , Saúde Bucal , Camundongos , Humanos , Bactérias Gram-Negativas/efeitos dos fármacosRESUMO
Pyroptosis has garnered increasing attention because of its ability to trigger robust antitumor immunity. Pyroptosis is initiated by the activation of inflammasomes, which are regulated by various organelles. The collaboration among organelles offers several protective mechanisms to prevent activation of the inflammasome, thereby limiting the induction of efficient pyroptosis. Herein, a multiorganelle homeostasis disruptor (denoted BLL) is constructed by encapsulating liposomes and bortezomib (BTZ) within a layered double hydroxide (LDH) nanocage to continuously activate inflammasomes for inducing efficient pyroptosis. In lysosomes, the negatively charged liposomes are released to recruit the NLRP3 inflammasomes through electrostatic interactions. ER stress is induced by BTZ to enhance the activation of the NLRP3 inflammasome. Meanwhile, the BLL nanocage exhibited H+-scavenging ability due to the weak alkalinity of LDH, thus disrupting the homeostasis of the lysosome and alleviating the degradation of the NLRP3 inflammasome by lysosomal-associated autophagy. Our results suggest that the BLL nanocage induces homeostatic imbalance in various organelles and efficient pyroptosis. We hope this work can provide new insights into the design of an efficient pyroptosis inducer by disrupting the homeostatic balance of multiple organelles and promote the development of novel antineoplastic platforms.
Assuntos
Homeostase , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Piroptose , Piroptose/efeitos dos fármacos , Inflamassomos/metabolismo , Inflamassomos/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Humanos , Camundongos , Bortezomib/farmacologia , Bortezomib/química , Lipossomos/química , Animais , Lisossomos/metabolismo , Lisossomos/efeitos dos fármacos , Hidróxidos/química , Hidróxidos/farmacologia , Nanoestruturas/química , Nanopartículas/químicaRESUMO
Purpose: The committed differentiation fate regulation has been a difficult problem in the fields of stem cell research, evidence showed that nanomaterials could promote the differentiation of stem cells into specific cell types. Layered double hydroxide (LDH) nanoparticles possess the regulation function of stem cell fate, while the underlying mechanism needs to be investigated. In this study, the process of embryonic stem cells (ESCs) differentiate to neural progenitor cells (NPCs) by magnesium aluminum LDH (MgAl-LDH) was investigated. Methods: MgAl-LDH with diameters of 30, 50, and 100 nm were synthesized and characterized, and their effects on the cytotoxicity and differentiation of NPCs were detected in vitro. Dot blot and MeRIP-qPCR were performed to detect the level of m6A RNA methylation in nanoparticles-treated cells. Results: Our work displayed that LDH nanoparticles of three different sizes were biocompatible with NPCs, and the addition of MgAl-LDH could significantly promote the process of ESCs differentiate to NPCs. 100 nm LDH has a stronger effect on promoting NPCs differentiation compared to 30 nm and 50 nm LDH. In addition, dot blot results indicated that the enhanced NPCs differentiation by MgAl-LDH was closely related to m6A RNA methylation process, and the major modification enzyme in LDH controlled NPCs differentiation may be the m6A RNA methyltransferase METTL3. The upregulated METTL3 by LDH increased the m6A level of Sox1 mRNA, enhancing its stability. Conclusion: This work reveals that MgAl-LDH nanoparticles can regulate the differentiation of ESCs into NPCs by increasing m6A RNA methylation modification of Sox1.
Assuntos
Diferenciação Celular , Nanopartículas , Células-Tronco Neurais , Diferenciação Celular/efeitos dos fármacos , Animais , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Camundongos , Nanopartículas/química , Metilação/efeitos dos fármacos , Hidróxidos/química , Hidróxidos/farmacologia , Metiltransferases/metabolismo , Metiltransferases/genética , Tamanho da Partícula , Células-Tronco Embrionárias/efeitos dos fármacos , Células-Tronco Embrionárias/citologia , Adenosina/farmacologia , Adenosina/química , Adenosina/análogos & derivados , Hidróxido de Alumínio/química , Hidróxido de Alumínio/farmacologia , Hidróxido de Magnésio/química , Hidróxido de Magnésio/farmacologiaRESUMO
Background: Breast cancer is the most common cancer in women and one of the leading causes of cancer death worldwide. Ferroptosis, a promising mechanism of killing cancer cells, has become a research hotspot in cancer therapy. Simvastatin (SIM), as a potential new anti-breast cancer drug, has been shown to cause ferroptosis of cancer cells and inhibit breast cancer metastasis and recurrence. The purpose of this study is to develop a novel strategy boosting ferroptotic cascade for synergistic cancer therapy. Methods: In this paper, iron base form of layered double hydroxide supported simvastatin (LDHs-SIM) was synthesized by hydrothermal co-precipitation method. The characterization of LDHs-SIM were assessed by various analytical techniques, including ultraviolet-visible (UV-vis) spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, and transmission electron microscopy (TEM). Biological activity, ferroptosis mechanism and biocompatibility were analyzed through in vivo and in vitro analysis, so as to evaluate its therapeutic effect on breast cancer. Results: The constructed LDHs-SIM nanosystem can not only release SIM through mevalonate (MVA) pathway, inhibit the expression of glutathione peroxidase 4 (GPX4), inhibit the expression of SLC7A11 and reduce the synthesis efficiency of GSH, but also promote the accumulation of Fe2+ in cells through the release of Fe3+, and increase the intracellular ROS content. In addition, LDHs-SIM nanosystem can induce apoptosis of breast cancer cells to a certain extent, and achieve the synergistic effect of apoptosis and ferroptosis. Conclusion: In the present study, we demonstrated that nanoparticles of layered double hydroxides (LDHs) loaded with simvastatin were more effective than a free drug at inhibiting breast cancer cell growth, In addition, superior anticancer therapeutic effects were achieved with little systemic toxicity, indicating that LDHs-SIM could serve as a safe and high-performance platform for ferroptosis-apoptosis combined anticancer therapy.
Assuntos
Apoptose , Neoplasias da Mama , Ferroptose , Hidróxidos , Sinvastatina , Ferroptose/efeitos dos fármacos , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Hidróxidos/química , Hidróxidos/farmacologia , Sinvastatina/farmacologia , Sinvastatina/química , Sinvastatina/administração & dosagem , Apoptose/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Nanopartículas/química , Sinergismo Farmacológico , Camundongos , Antineoplásicos/farmacologia , Antineoplásicos/química , Camundongos Nus , Camundongos Endogâmicos BALB C , Células MCF-7 , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismoRESUMO
The development of cost-effective and eco-friendly fertilizers is crucial for enhancing iron (Fe) uptake in crops and can help alleviate dietary Fe deficiencies, especially in populations with limited access to meat. This study focused on the application of MgFe-layered double hydroxide nanoparticles (MgFe-LDHs) as a potential solution. We successfully synthesized and characterized MgFe-LDHs and observed that 1-10 mg/L MgFe-LDHs improved cucumber seed germination and water uptake. Notably, the application of 10 mg/L MgFe-LDHs to roots significantly increased the seedling emergence rate and growth under low-temperature stress. The application of 10 mg/L MgFe-LDHs during sowing increased the root length, lateral root number, root fresh weight, aboveground fresh weight, and hypocotyl length under low-temperature stress. A comprehensive analysis integrating plant physiology, nutrition, and transcriptomics suggested that MgFe-LDHs improve cold tolerance by upregulating SA to stimulate CsFAD3 expression, elevating GA3 levels for enhanced nitrogen metabolism and protein synthesis, and reducing levels of ABA and JA to support seedling emergence rate and growth, along with increasing the expression and activity of peroxidase genes. SEM and FTIR further confirmed the adsorption of MgFe-LDHs onto the root hairs in the mature zone of the root apex. Remarkably, MgFe-LDHs application led to a 46% increase (p < 0.05) in the Fe content within cucumber seedlings, a phenomenon not observed with comparable iron salt solutions, suggesting that the nanocrystalline nature of MgFe-LDHs enhances their absorption efficiency in plants. Additionally, MgFe-LDHs significantly increased the nitrogen (N) content of the seedlings by 12% (p < 0.05), promoting nitrogen fixation in the cucumber seedlings. These results pave the way for the development and use of LDH-based Fe fertilizers.
Assuntos
Temperatura Baixa , Cucumis sativus , Ferro , Plântula , Cucumis sativus/crescimento & desenvolvimento , Cucumis sativus/metabolismo , Cucumis sativus/efeitos dos fármacos , Plântula/crescimento & desenvolvimento , Plântula/metabolismo , Plântula/efeitos dos fármacos , Ferro/metabolismo , Raízes de Plantas/metabolismo , Raízes de Plantas/crescimento & desenvolvimento , Germinação/efeitos dos fármacos , Hidróxidos/farmacologia , Hidróxidos/metabolismo , Fertilizantes , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Nanopartículas/química , Estresse Fisiológico , Magnésio/metabolismoRESUMO
The foreseen increasing application of copper-based nanomaterials (Cu-NMs), replacing or complementing existing Cu-agrochemicals, may negatively impact the soil microbiome. Thus, we studied the effects on soil microbiome function and composition of nano copper oxide (nCuO) or copper hydroxide NMs in a commercial (Kocide®3000) or a lab-synthetized formulation (nCu(OH)2) or bulk copper hydroxide (Cu(OH)2-B), at the commonly recommended Cu dose of 50 mg(Cu)kg-1 soil. Microbial responses were studied over 28 days in a designed indoor mesocosm. On day-28, in comparison to non-treated soil (CT), all Cu-treatments led to a reduction in dehydrogenase (95% to 68%), arylsulfatase (41% to 27%), and urease (40% to 20%) activity. There was a 32% increase in the utilization of carbon substrates in the nCuO-treatment and an increased abundance of viable bacteria in the nCu(OH)2-treatment (75% of heterotrophic and 69% of P-solubilizing bacteria). The relative abundance of Acidobacteria [Kocide®3000, nCuO, and Cu(OH)2-B treatments] and Flavobacteriia [nCu(OH)2-treatment] was negatively affected by Cu exposure. The abundance of Cu-tolerant bacteria increased in soils treated with Kocide®3000 (Clostridia) and nCu(OH)2 (Gemmatimonadetes). All Cu-treated soils exhibited a reduced abundance of denitrification-related genes (0.05% of nosZ gene). The DTPA-extractable pool of ionic Cu(II) varied among treatments: Cu(OH)2-B > Kocide®3000 â¼ nCuO>nCu(OH)2, which may explain changes on the soil microbiome composition, at the genera and OTU levels. Thus, our study revealed that Cu-materials (nano and bulk) influence the soil microbiome with implications on its ecological role. It highlights the importance of assessing the impact of Cu-materials under dynamic and complex exposure scenarios and emphasizes the need for specific regulatory frameworks for NMs.
Assuntos
Agricultura , Cobre , Microbiota , Microbiologia do Solo , Cobre/farmacologia , Microbiota/efeitos dos fármacos , Solo/química , Bactérias/efeitos dos fármacos , Bactérias/genética , Bactérias/metabolismo , Hidróxidos/química , Hidróxidos/farmacologia , Nanopartículas Metálicas/química , Nanoestruturas/químicaRESUMO
Antifungal resistance has become a very serious concern, and Candida albicans is considered one of the most opportunistic fungal pathogens responsible for several human infections. In this context, the use of new antifungal agents such as zinc-based layered double hydroxides to fight such fungal pathogens is considered one possible means to help limit the problem of antifungal resistance. In this study, we show that ZnAl LDH nanoparticles exhibit remarkable antifungal properties against C. albicans and cause serious cell wall damage, as revealed by growth tests and atomic force microscopy (AFM) imaging. To further link the antifungal activity of ZnAl LDHs to their adhesive behaviors toward C. albicans cells, AFM-based single-cell spectroscopy and single-particle force spectroscopy were used to probe the nanoscale adhesive interactions. The force spectroscopy analysis revealed that antimicrobial ZnAl LDHs exhibit specific surface interactions with C. albicans cells, demonstrating remarkable force magnitudes and adhesion frequencies in comparison with non-antifungal negative controls, e.g., Al-coated substrates and MgAl LDHs, which showed limited interactions with C. albicans cells. Force signatures suggest that such adhesive interactions may be attributed to the presence of agglutinin-like sequence (Als) adhesive proteins at the cell wall surface of C. albicans cells. Our findings propose the presence of a strong correlation between the antifungal effect provided by ZnAl LDHs and their nanoscale adhesive interactions with C. albicans cells at both the single-cell and single-particle levels. Therefore, ZnAl LDHs could interact with C. albicans fungal pathogens by specific adhesive interactions through which they adhere to fungal cells, leading to their damage and subsequent growth inhibition.
Assuntos
Antifúngicos , Candida albicans , Compostos de Zinco , Humanos , Antifúngicos/farmacologia , Hidróxidos/farmacologia , Hidróxidos/química , Zinco/farmacologia , Zinco/química , Análise EspectralRESUMO
Tissue-engineered poly(l-lactide) (PLLA) scaffolds have been widely used to treat bone defects; however, poor biological activities have always been key challenges for its further application. To address this issue, introducing bioactive drugs or factors is the most commonly used method, but there are often many problems such as high cost, uncontrollable and monotonous drug activity, and poor bioavailability. Here, a drug-free 3D printing PLLA scaffold with a triple-effect combination induced by surface-modified copper-doped layered double hydroxides (Cu-LDHs) is proposed. In the early stage of scaffold implantation, Cu-LDHs exert a photothermal therapy (PTT) effect to generate high temperature to effectively prevent bacterial infection. In the later stage, Cu-LDHs can further have a mild hyperthermia (MHT) effect to stimulate angiogenesis and osteogenic differentiation, demonstrating excellent vascularization and osteogenic activity. More importantly, with the degradation of Cu-LDHs, the released Cu2+ and Mg2+ provide an ion microenvironment effect and further synergize with the MHT effect to stimulate angiogenesis and osteogenic differentiation, thus more effectively promoting the healing of bone tissue. This triple-effect combined scaffold exhibits outstanding antibacterial, osteogenic, and angiogenic activities, as well as the advantages of low cost, convenient procedure, and long-term efficacy, and is expected to provide a promising strategy for clinical repair of bone defects.
Assuntos
Osteogênese , Alicerces Teciduais , Cobre/farmacologia , Regeneração Óssea , Hidróxidos/farmacologia , Impressão TridimensionalRESUMO
Combining targeted therapy and immunotherapy brings hope for a complete cancer cure. Due to their selective colonization and immune activation capacity, some bacteria have the potential to realize targeted immunotherapy. Herein, a biohybrid system was designed and synthesized by cladding NO3--intercalated cobalt aluminum layered double hydroxides (LDH) on anaerobic Propionibacterium acnes (PA) (PA@LDH). In this system, the covering of LDH reduces the pathogenicity of PA to normal tissues and alters its surface charge for prolonged in vivo circulation. Once the tumor site is reached, the acid-responsive degradation of LDH enables PA exposure. PA can colonize and convert nitrate ions to nitric oxide (NO) through denitrification. Then, NO reacts with intracellular O2·- to produce toxic reactive nitrogen species ONOO- and induce tumor cell apoptosis. In addition, cobalt ions released from LDH can inhibit the activity of superoxide dismutase (SOD), thus increasing the level of O2·- and further enhancing the antitumor effect. Moreover, PA exposure activates M2-to-M1 macrophage polarization and a range of immune responses, thereby achieving a sustained antitumor activity. In vitro and in vivo results reveal that the biohybrid system eliminates solid tumors and inhibits tumor metastasis effectively. Overall, the biohybrid strategy provides a new avenue for realizing simultaneous immunotherapy and targeted therapy.
Assuntos
Carvão Mineral , Neoplasias , Humanos , Hidróxidos/farmacologia , Hidróxido de Alumínio , Cobalto/farmacologia , Bactérias , ImunoterapiaRESUMO
Tumor-associated macrophages (TAMs) are important immune cells in the tumor microenvironment (TME). The polar plasticity of TAMs makes them important targets for improving the immunosuppressive microenvironment of tumors. The previous study reveals that layered double hydroxides (LDHs) can effectively promote the polarization of TAMs from the anti-inflammatory M2 type to the pro-inflammatory M1 type. However, their mechanisms of action remain unexplored. This study reveals that LDHs composed of different cations exhibit distinct abilities to regulate the polarity of TAMs. Compared to Mg-Fe LDH, Mg-Al LDH has a stronger ability to promote the repolarization of TAMs from M2 to M1 and inhibit the formation of myeloid-derived suppressor cells (MDSCs). In addition, Mg-Al LDH restrains the growth of tumors in vivo and promotes the infiltration of activated immune cells into the TME more effectively. Interestingly, Mg-Al LDH influences the autophagy of TAMs; this negatively correlates with the pro-inflammatory ability of TAMs. Therefore, LDHs exert their polarization ability by inhibiting the autophagy of TAMs, and this mechanism might be related to the ionic composition of LDHs. This study lays the foundation for optimizing the performance of LDH-based immune adjuvants, which display excellent application prospects for tumor immunotherapy.
Assuntos
Autofagia , Macrófagos Associados a Tumor , Adjuvantes Imunológicos , Hidróxidos/farmacologiaRESUMO
Bacterial infections have been a major threat to human health. Especially, Gram-negative (G-) bacterial infections have been an increasing problem worldwide. The overuse of antibiotics leads to an emergence of drug resistance, and thus the development of novel antimicrobial agents is important, particularly against G- bacteria. Nanozymes use reactive oxygen species (ROS) to kill bacteria, reducing the risk of bacterial resistance and providing new opportunities to meet the challenges of strain selectivity. Here, we synthesized NiCo layered double hydroxide (LDH) nanozymes, which exhibit selective antibacterial activity based on their peroxide-like (POD-like) activity. To obtain the highest antibacterial activity, the POD-like activity of NiCo LDH nanozyme was further optimized by tuning the ratio of nickel and cobalt, and Ni4Co6 LDHs showed the highest POD activity and antibacterial activity. More importantly, Ni4Co6 LDHs can achieve selective sterilization of G- bacteria due to their electrostatic adsorption and hydrophilic interactions with the bacterial cell wall. Animal experiments further indicated that the healing of G- bacteria-infected wounds was effectively promoted without damaging their normal biological tissues. In conclusion, we provide a selective antibacterial agent through a simple strategy, which provides a new direction for the application of nanozymes.
Assuntos
Infecções Bacterianas , Animais , Humanos , Bactérias Gram-Negativas , Bactérias , Antibacterianos/farmacologia , Cicatrização , Hidróxidos/farmacologiaRESUMO
Lycopene is a natural compound with one of the highest antioxidant activities. Its consumption is associated with lower risks in lung cancer and chronic obstructive pulmonary disease, for example. Experimentally, a murine model demonstrated the ingestion of lycopene, which reduced the damage in lungs caused by cigarette smoke. Since lycopene is highly hydrophobic, its formulations in supplements and preparations for laboratory assays are based on oils, additionally, bioavailavility is low. We developed a lycopene layered double hydroxide (Lyc-LDH) composite, which is capable of transporting lycopene aqueous media. Our objective was to evaluate the cytotoxicity of Lyc-LDH and the intra-cellular production of reactive oxygen species (ROS) in J774A.1 cells. Also, in vivo assays were conducted with 50 male C57BL/6 mice intranasally treated with Lyc-LDH 10 mg/kg (LG10), Lyc-LDH 25 mg/kg (LG25) and Lyc-LDH 50 mg/kg (LG50) during five days compared against a vehicle (VG) and control (CG) group. The blood, bronchoalveolar lavage fluid (BALF) and lung tissue were analyzed. The results revealed that Lyc-LDH composite attenuated intracellular ROS production stimulated with lipopolysacharide. In BALF, the highest doses of Lyc-LDH (LG25 and LG50) promoted influx of macrophages, lymphocytes, neutrophils and eosinophils compared to CG and VG. Also, LG50 increased the levels of IL-6 and IL-13, and promoted the redox imbalance in the pulmonary tissue. On the contrary, low concentrations did not produce significative effects. In conclusion, our results suggest that intranasal administration of high concentrations of Lyc-LDH induces inflammation as well as redox status changes in the lungs of healthy mice, however, results with low concentrations open a promising way to study LDH composites as vehicles for intranasal administration of antioxidant coadjuvants.
Assuntos
Antioxidantes , Estresse Oxidativo , Camundongos , Masculino , Animais , Licopeno/farmacologia , Antioxidantes/farmacologia , Espécies Reativas de Oxigênio , Camundongos Endogâmicos C57BL , Pulmão/metabolismo , Hidróxidos/farmacologiaRESUMO
Bacterial resistance to conventional antibiotics is a serious challenge that requires novel antibacterial agents. Moreover, wastewater from dairy farms might contain countless number of pathogens, organic contaminants and heavy metals that consider a threat to the terrestrial and aquatic environment. Therefore, the development of cost-effective, highly operation-convenient, recyclable multifunctional antimicrobial agents became an urgent necessity. Layered double hydroxides (LDH) have shown promising results as antibacterial agents. However, more work is required to further investigate and improve the antimicrobial performance of LDH structures against pathogens. In this study three Zn-Fe based LDH were investigated for real dairy wastewater disinfection. The three LDH samples were cobalt substituted Zn-Fe LDH (CoZnFe), magnesium substituted Zn-Fe LDH (MgZnFe) and MgZnFe-Triazol LDH (MgZnFe-Tz) nanocomposite. Seventy-five wastewater samples were collected from a dairy farm sewage system. The sensitivity of isolated pathogens was tested against two commonly used disinfectants (Terminator and TH4) and was assessed against the three LDH samples at different concentrations. The overall prevalence of S. agalactiae, S. dysgalactiae and Staph. aureus was significantly at 80.0% (P-value = 0.008, X2 = 9.700). There was variable degree of resistance to the tested disinfectants, whereas the antimicrobial activity of CoZnFe LDH was increased significantly at a concentration of 0.005 mg/L followed by MgZnFe LDH while MgZnFe-Tz LDH showed minor antibacterial potency. It was concluded that CoZnFe LDH showed a better biocidal activity in killing the isolated resistant pathogens, making it a good choice tool in combating the zoonotic microbes in wastewater sources.
Assuntos
Desinfetantes , Águas Residuárias , Desinfecção , Hidróxidos/farmacologia , Hidróxidos/química , Antibacterianos/farmacologia , Antibacterianos/química , Staphylococcus aureus , Zinco/química , Desinfetantes/farmacologiaRESUMO
The committed differentiation of stem cells into neurons is a promising therapeutic strategy for neurological diseases. Predifferentiation of transplanted stem cells into neural precursors could enhance their utilization and control the direction of differentiation. Embryonic stem cells with totipotency can differentiate into specific nerve cells under appropriate external induction conditions. Layered double hydroxide (LDH) nanoparticles have been proven to regulate the pluripotency of mouse ESCs (mESCs), and LDH could be used as carrier in neural stem cells for nerve regeneration. Hence, we sought to study the effects of LDH without loaded factors on mESCs neurogenesis in this work. A series of characteristics analyses indicated the successful construction of LDH nanoparticles. LDH nanoparticles that may adhere to the cell membranes had insignificant effect on cell proliferation and apoptosis. The enhanced differentiation of mESCs into motor neurons by LDH was systematically validated by immunofluorescent staining, quantitative real-time PCR analysis and western blot analysis. In addition, transcriptome sequencing analysis and mechanism verification elucidated the significant regulatory roles of focal adhesion signaling pathway in the enhanced mESCs neurogenesis by LDH. Taken together, the functional validation of inorganic LDH nanoparticles promoting motor neurons differentiation provide a novel strategy and therapeutic prospect for the clinical transition of neural regeneration.