Boosting the sonodynamic performance of CoBiMn-layered double hydroxide nanoparticles via tumor microenvironment regulation for ultrasound imaging-guided sonodynamic therapy.

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.

Enhancing iron content and growth of cucumber seedlings with MgFe-LDHs under low-temperature stress.

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.

Highly Crystalline Copper Aluminum-Layered Double Hydroxides with Intrinsic Fenton-Like Catalytic Activity for Robust Oral Health Management.

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.

Size-Optimized Layered Double Hydroxide Nanoparticles Promote Neural Progenitor Cells Differentiation of Embryonic Stem Cells Through the Regulation of M6A Methylation.

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.

Synergistic Effect of Layered Double Hydroxides Nanodosage Form to Induce Apoptosis and Ferroptosis in Breast Cancer.

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.

An Alkaline Nanocage Continuously Activates Inflammasomes by Disrupting Multiorganelle Homeostasis for Efficient Pyroptosis.

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.

Responses of soil microbiome to copper-based materials (nano and bulk) for agricultural applications: An indoor-mesocosm experiment.

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 âˆ¼ 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.

Understanding the nanoscale adhesion forces between the fungal pathogen Candida albicans and antimicrobial zinc-based layered double hydroxides using single-cell and single-particle force spectroscopy.

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.

3D Printing Drug-Free Scaffold with Triple-Effect Combination Induced by Copper-Doped Layered Double Hydroxides for the Treatment of Bone Defects.

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.

Integration of CoAl-Layered Double Hydroxides on Commensal Bacteria to Enable Targeted Tumor Inhibition and Immunotherapy.

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.

Blocked Autophagy is Involved in Layered Double Hydroxide-Induced Repolarization and Immune Activation in Tumor-Associated Macrophages.

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.

NiCo LDH nanozymes with selective antibacterial activity against Gram-negative bacteria for wound healing.

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.

Effects of a lycopene-layered double hydroxide composite administration in cells and lungs of adult mice.

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.

Antimicrobial properties of promising Zn-Fe based layered double hydroxides for the disinfection of real dairy wastewater effluents.

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.

The enhanced generation of motor neurons from mESCs by MgAl layered double hydroxide nanoparticles.

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.

Sequentially activating macrophages M1 and M2 phenotypes by lipopolysaccharide-containing Mg-Fe layered double hydroxides coating on the Ti substrate.

As cells of innate immunity, macrophages are a class of innate immune cells existing in almost all tissues and play a crucial role in bone repair. However, it remains a challenge to modulate the sequential activation of the deferent phenotypes in macrophage when designing the titanium (Ti) implants. In this study, the Mg-Fe layered double hydroxides (LDHs) was coated on Ti substrate through hydrothermal treatment. Further on lipopolysaccharide (LPS) was introduced onto the LDHs through adsorption and ions exchange. The adsorption efficiency of the coating on LPS reached 72.8% in 24 h due to the anion exchange and electrostatic interactions between the LPS and the LDH layers in deionized water. The LDHs-LPS coating released a large amount of LPS in the early stage, which induced macrophages into M1 phenotype via activating TLR-4 → MyD88 and TLR-4 → Ticam-1/2 signal pathways. Subsequently, the M1 macrophages were transformed into M2 phenotype by regulating the integrin α5ß1 of cells by the nanostructures, wetting angle and Mg2+ of the coating. The LDHs-LPS coating endows Ti with the ability of stage immunomodulation, indicating the positive osteoimmunomodulatory property.

Construction and Evaluation of Hyaluronic Acid-Coated Flurbiprofen-Layered Double Hydroxide Ocular Drug Delivery System.

In this study, flurbiprofen (FB) was selected as the model drug, and hyaluronic acid-coated flurbiprofen-layered double hydroxide ophthalmic drug delivery system (HA-FB-LDH) was designed and prepared. In this system, the model drug flurbiprofen was intercalated in layered double hydroxide and coated with hyaluronic acid (HA), so as to prolong the corneal residence time and increase the corneal permeability of the drug. Layered double hydroxide (LDH) was prepared by alcohol-water coprecipitation method. Through single factor investigation, the optimum preparation conditions were obtained as follows: The Mg/Al ratio was 2:1, the reaction pH was 11.0, the hydrothermal reaction time was 24 h, and the hydrothermal reaction temperature was 100°C. Under these conditions, the particle size of LDH was 116.4 ± 0.8 nm, the potential was 42.2 ± 1.2 mV, and a relatively regular crystal structure could be had. Then FB was intercalated into the LDH layer to prepare flurbiprofen-layered double hydroxide (FB-LDH). In the end, HA-FB-LDH was prepared by the stirring-ultrasonic method, in which through prescription screening, the molecular weight of HA was 200-400 kDa and the concentration of HA solution was 1.25 mg·mL -1, the final particle size of HA-FB-LDH was 185.8 ± 3.3 nm, and potential of - 31.4 ± 0.7 mV. The successful loading of FB and the coating of HA were verified by XRD, FTIR, TGA, TEM, and other characterization methods. The results of in vitro stability experiment indicated that the coating of HA could significantly enhance the stability of LDH in the presence of electrolytes. The in vitro release results suggested that the cumulative release amounts of FB-LDH and HA-FB-LDH within 12 h were 92.99 ± 0.37% and 74.82 ± 0.29% respectively, showing a certain sustained release effect. At the same time, the release mechanism of FB-LDH was preliminarily explored by in vitro release experiment, which proved that the release mechanism of FB-LDH was mainly ion exchange. The results of in vivo ocular irritation experiments demonstrated that the ophthalmic preparation studied in this paper was safe and non-irritating. The results of tear pharmacokinetics in rabbits showed that the area under the curve(AUC), the average residence time (MRT), and the highest concentration (Cmax) in tears in the HA-FB-LDH group were 4.43, 4.48, and 2.27 times higher than those in eye drops group separately. Furthermore, the AUC of the HA-FB-LDH group was 1.48 times higher than that of the FB-LDH group. The above results suggested that HA-FB-LDH could improve the precorneal residence time. The results of aqueous humor pharmacokinetics in rabbits indicated that the AUC, MRT, and maximum concentration (Cmax) in aqueous humor in the HA-FB-LDH group were 6.88, 2.15, and 4.08 times of those in the eye drop group respectively. Additionally, the AUC and MRT of the HA-FB-LDH group were 1.55 and 1.63 times those of the FB-LDH group separately. These mentioned findings verified that HA-FB-LDH could enhance the corneal permeability of the drug. The fluorescent substance-fluoresce isothiocyanate (FITC) was substituted for FB intercalation in LDH for in vitro tissue imaging study of rabbits, whose results stated clearly that FITC-LDH and HA-FITC-LDH could both prolong the precorneal residence time of drugs, and HA-FITC-LDH could increase the corneal permeability of the drug to a certain extent. To sum up, HA-FB-LDH, which can overcome the shortcomings of low bioavailability of traditional eye drops to a certain degree, is a safe and effective ophthalmic drug delivery system.

The impact of an alkasite restorative material on the pH of Streptococcus mutans biofilm and dentin remineralization: an in vitro study.

BACKGROUND: It has been claimed that an alkasite restorative material can neutralize acids produced by cariogenic bacteria from released hydrogen ions and enable to remineralization via calcium and fluoride ions. However, there is no evidence to support this assertion. Therefore, the aims of this study were to investigate the effect of the alkasite restorative material on the pH of Streptococcus mutans biofilm and dentin hardness. METHODS: Streptococcus mutans biofilms were formed on Filtek™ Z350 (FZ, a resin composite) and Cention® N (CN, the alkasite restorative material) and their pH determined after 24 h. Hydroxide, fluoride, and calcium-ions released from the materials were determined at 6 h, 1, 3, 7, 14, and 28 days. Dentin specimens were prepared from 14 human molars and divided into four quadrants. Quadrant 1 was a sound dentin control, quadrants 2-4 were chemically demineralized, and a cylinder of FZ and CN placed on the surfaces of quadrants 2 and 4, respectively. The microhardness of quadrants 1 and 3 were measured at depths of 20, 40, and 60 µm from the occlusal surface, and similarly of quadrants 2 and 4, after 30 days. Independent t-test, Mann-Whitney-U, and repeated-measure-ANOVA were used for data analysis. RESULTS: The pH of biofilm on CN (4.45) was significantly higher (p < 0.05) than that on FZ (4.06). The quantity of all ions released from CN was significantly higher than from FZ. The hardness of demineralized dentin under CN was significantly higher than that of demineralized dentin at all depths, and higher than that of demineralized dentin under FZ at 20 and 40 µm. CONCLUSIONS: CN released hydroxide, fluoride, and calcium ions, which was associated with raising the biofilm pH and the hardness of demineralized dentin. All results indicated that CN had the potential to reduce the incidence of secondary caries.

Understanding the role of surface interactions in the antibacterial activity of layered double hydroxide nanoparticles by atomic force microscopy.

Understanding the mechanisms of the interactions between zinc-based layered double hydroxides (LDHs) and bacterial surfaces is of great importance to improve the efficiency of these antibiotic-free antibacterial agents. In fact, the role of surface interactions in the antibacterial activity of zinc-based LDH nanoparticles compared to that of dissolution and generation of reactive oxygen species (ROS) is still not well documented. In this study, we show that ZnAl LDH nanoparticles exhibit a strong antibacterial effect against Staphylococcus aureus by inducing serious cell wall damages as revealed by the antibacterial activity tests and atomic force microscopy (AFM) imaging, respectively. The comparison of the antibacterial properties of ZnAl LDH nanoparticles and micron-sized ZnAl LDHs also demonstrated that the antibacterial activity of Zn-based LDHs goes beyond the simple dissolution into Zn2+ antibacterial ions. Furthermore, we developed an original approach to functionalize AFM tips with LDH films in order to probe their interactions with living S. aureus cells by means of AFM-based force spectroscopy (FS). The force spectroscopy analysis revealed that antibacterial ZnAl LDH nanoparticles show specific recognition of S. aureus cells with high adhesion frequency and remarkable force magnitudes. This finding provides a first insight into the antibacterial mechanism of Zn-based LDHs through direct surface interactions by which they are able to recognize and adhere to bacterial surfaces, thus damaging them and leading to subsequent growth inhibition.

Promoted removal of phosphate by layered double hydroxides combined with bacteria: Application of novel carriers in biofilm reactor.

Layered double hydroxides (LDHs) were used as carriers for the microbial consortium in sequencing biofilm batch reactor (SBBR) without inoculation to promote the removal of phosphate. The adsorption capacity of [Zn-Al]-LDH was significantly better than that of [Mg-Al]-LDH. The pollutants removal performance and behavior of microorganisms in LDH-SBBRs were also investigated. LDH-SBBRs showed improved removal efficiencies of COD, phosphate and TP with a low C/N ratio. Microscopic images show that biofilm formed rapidly in LDH-SBBRs. SEM-EDS detected abundant carbon and phosphorus, implying that biomass and phosphorus accumulate on LDH carriers. The microbial compositions of the three SBBRs indicate that the LDHs carriers improved the biodiversity of biofilm in the bioreactors. Synergistic effects of adsorption and biodegradation between well-structured LDHs and microorganisms led to an improved phosphate removal performance of LDH-SBBR. The results also demonstrate that [Zn-Al]-LDH carrier is the best for improving SBBR phosphate removal.