Gadolinium Doped Layered Double Hydroxides for Simultaneous Drug Delivery and Magnetic Resonance Imaging

In this study, gadolinium (Gd) doped MgAl layered double hydroxides (LDHs) were synthesized via a ‘bottom-up’ method and fully characterized by X-ray diffraction, infrared spectroscopy and relaxivity measurements. Two cytotoxic agents were then intercalated via ion-exchange. X-ray diffraction patterns exhibit expanded interlayer spacings as a result of successful drug intercalation. Infrared spectra also showed characteristic peaks of the incorporated methotrexate (MTX) or 5-fluorouracil (5-FU). The LDHs were found to be highly stable under physiological conditions, while in acidic conditions a small proportion of Gd was freed into the immersion medium. Dissolution tests revealed that both 5FU and MTX were rapidly released from the LDH carrier. The longitudinal relaxivity of Gd-LDHs remains largely stable during drug release over 24 h, and was higher in acidic environments. Overall, the drug-loaded Gd-LDH systems prepared in this study could serve as pH-sensitive theranostic platforms for MRI-guided anti-cancer therapy

Gadolinium Doped Layered Double Hydroxides for Simultaneous Drug Delivery and Magnetic Resonance Imaging

In this study, gadolinium (Gd) doped MgAl layered double hydroxides (LDHs) were synthesized via a ‘bottom-up’ method and fully characterized by X-ray diffraction, infrared spectroscopy and relaxivity measurements. Two cytotoxic agents were then intercalated via ion-exchange. X-ray diffraction patterns exhibit expanded interlayer spacings as a result of successful drug intercalation. Infrared spectra also showed characteristic peaks of the incorporated methotrexate (MTX) or 5-fluorouracil (5-FU). The LDHs were found to be highly stable under physiological conditions, while in acidic conditions a small proportion of Gd was freed into the immersion medium. Dissolution tests revealed that both 5FU and MTX were rapidly released from the LDH carrier. The longitudinal relaxivity of Gd-LDHs remains largely stable during drug release over 24 h, and was higher in acidic environments. Overall, the drug-loaded Gd-LDH systems prepared in this study could serve as pH-sensitive theranostic platforms for MRI-guided anti-cancer therapy.</p

Ternary NiCoTi-layered double hydroxide nanosheets as a pH-responsive nanoagent for photodynamic/chemodynamic synergistic therapy

Combining photodynamic therapy (PDT) with chemodynamic therapy (CDT) has been proven to be a promising strategy to improve the treatment efficiency of cancer, because of the synergistic therapeutic effect arising between the two modalities. Herein, we report an inorganic nanoagent based on ternary NiCoTi-layered double hydroxide (NiCoTi-LDH) nanosheets to realize highly efficient photodynamic/chemodynamic synergistic therapy. The NiCoTi-LDH nanosheets exhibit oxygen vacancy-promoted electron-hole separation and photogenerated hole-induced O2-independent reactive oxygen species (ROS) generation under acidic circumstances, realizing in situ pH-responsive PDT. Moreover, due to the effective conversion between Co^{3+} and Co^{2+} caused by photogenerated electrons, the NiCoTi-LDH nanosheets catalyze the release of hydroxyl radicals (∙OH) from H2O2 through Fenton reactions, resulting in CDT. Laser irradiation enhances the catalyzed ability of the NiCoTi-LDH nanosheets to promote the ROS generation, resulting in a better performance than TiO_{2} nanoparticles at pH 6.5. In vitro and in vivo experimental results show conclusively that NiCoTi-LDH nanosheets plus irradiation lead to efficient cell apoptosis and significant inhibition of tumor growth. This study reports a new pH-responsive inorganic nanoagent with oxygen vacancy-promoted photodynamic/chemodynamic synergistic performance, offering a potentially appealing clinical strategy for selective tumor elimination

Combined analysis of mRNA and miRNA transcriptomes reveals the regulatory mechanism of Xanthomonas arboricola pv pruni resistance in Prunus persica

Abstract Background Peach bacterial shot hole, caused by Xanthomonas arboricola pv pruni (Xap), is a global bacterial disease that poses a threat to the yield and quality of cultivated peach trees (Prunus persica). Results This study compared the mRNA and miRNA profiles of two peach varieties, ‘Yanbao’ (resistant) and ‘Yingzui’ (susceptible), after inoculation with Xap to identify miRNAs and target genes associated with peach tree resistance. mRNA sequencing results revealed that in the S0-vs-S3 comparison group, 1574 genes were upregulated and 3975 genes were downregulated. In the R0-vs-R3 comparison group, 1575 genes were upregulated and 3726 genes were downregulated. Through miRNA sequencing, a total of 112 known miRNAs belonging to 70 miRNA families and 111 new miRNAs were identified. Notably, some miRNAs were exclusively expressed in either resistant or susceptible varieties. Additionally, 59 miRNAs were downregulated and 69 miRNAs were upregulated in the R0-vs-R3 comparison group, while 46 miRNAs were downregulated and 52 miRNAs were upregulated in the S0-vs-S3 comparison group. Joint analysis of mRNA and miRNA identified 79 relationship pairs in the S0-vs-S3 comparison group, consisting of 48 miRNAs and 51 target genes. In the R0-vs-R3 comparison group, there were 58 relationship pairs, comprising 28 miRNAs and 20 target genes. Several target genes related to resistance, such as SPL6, TIFY6B, and Prupe.4G041800_v2.0.a1 (PPO), were identified through literature reports and GO/KEGG enrichment analysis. Conclusion In conclusion, this study discovered several candidate genes involved in peach tree resistance by analyzing differential expression of mRNA and miRNA. These findings provide valuable insights into the mechanisms underlying resistance to Xap in peach trees

Additional file 1 of Combined analysis of mRNA and miRNA transcriptomes reveals the regulatory mechanism of Xanthomonas arboricola pv pruni resistance in Prunus persica

Supplementary Material 1

Global, Regional, and National Burdens of Ischemic Heart Disease Attributable to Smoking From 1990 to 2019

Background This study was conducted to estimate the distribution of and changes in the global disease burden of ischemic heart disease attributable to smoking between 1990 and 2019. Methods and Results Data used in this study come from the GBD 2019 (Global Burden of Disease Study 2019). Age‐standardized rates and estimated annual percentage change of age‐standardized rates were used to describe this burden and its changing trend. Pearson's correlation coefficient was used to evaluate the correlation between the sociodemographic index and changing trend. From 1990 to 2019, the burden of ischemic heart disease attributable to smoking has shown a downward trend globally; estimated annual percentage changes of age‐standardized mortality rates and age‐standardized disability‐adjusted life‐years rates were −2.012 (95% CI, −2.068 to −1.956) and −1.907 (95% CI, −1.975 to −1.838). Nineteen countries experienced an increase in disease burden, and the changes in 17 countries were not statistically significant. In addition, this burden was higher in men and older age groups. Estimated annual percentage change of the age‐standardized rates of this burden were negatively correlated with the sociodemographic index. Conclusions Although the burden of ischemic heart disease attributable to smoking has decreased in >80% of countries or regions in the past 30 years, it has remained a significant issue in low‐ and middle‐income countries, particularly among men and elderly populations. Therefore, active tobacco control measures, focusing on key populations, are required to reduce the associated burden of ischemic heart disease, especially in those countries or regions with increasing prevalence and disease burden

Layered double hydroxide-based nanomaterials for biomedical applications

Against the backdrop of increased public health awareness, inorganic nanomaterials have been widely explored as promising nanoagents for various kinds of biomedical applications. Layered double hydroxides (LDHs), with versatile physicochemical advantages including excellent biocompatibility, pH-sensitive biodegradability, highly tunable chemical composition and structure, and ease of composite formation with other materials, have shown great promise in biomedical applications. In this review, we comprehensively summarize the recent advances in LDH-based nanomaterials for biomedical applications. Firstly, the material categories and advantages of LDH-based nanomaterials are discussed. The preparation and surface modification of LDH-based nanomaterials, including pristine LDHs, LDH-based nanocomposites and LDH-derived nanomaterials, are then described. Thereafter, we systematically describe the great potential of LDHs in biomedical applications including drug/gene delivery, bioimaging diagnosis, cancer therapy, biosensing, tissue engineering, and anti-bacteria. Finally, on the basis of the current state of the art, we conclude with insights on the remaining challenges and future prospects in this rapidly emerging field

Recent advances in two-dimensional nanomaterials for bone tissue engineering

Over the last decades, bone tissue engineering has increasingly become a research focus in the field of biomedical engineering, in which biomaterials play an important role because they can provide both biomechanical support and osteogenic microenvironment in the process of bone regeneration. Among these biomaterials, two-dimensional (2D) nanomaterials have recently attracted considerable interest owing to their fantastic physicochemical and biological properties including great biocompatibility, excellent osteogenic capability, large specific surface area, and outstanding drug loading capacity. In this review, we summarize the state-of-the-art advances in 2D nanomaterials for bone tissue engineering. Firstly, we introduce the most explored biomaterials used in bone tissue engineering and their advantages. We then highlight the advances of cutting-edge 2D nanomaterials such as graphene and its derivatives, layered double hydroxides, black phosphorus, transition metal dichalcogenides, montmorillonite, hexagonal boron nitride, graphite phase carbon nitride, and transition metal carbonitrides (MXenes) used in bone tissue engineering. Finally, the current challenges and future prospects of 2D nanomaterials for bone tissue regeneration in process of clinical translation are discussed

Thermo-responsive nano-in-micro particles for MRI-guided chemotherapy

In this work, we develop nano-in-micro thermo-responsive microspheres as theranostic systems for anti-cancer hyperthermia. Firstly, layered double hydroxide (LDH) nanoparticles were synthesized and subsequently loaded with the chemotherapeutic agents methotrexate (MTX) or 5-fluorouracil (5FU). The drug-loaded LDH particles were then co-encapsulated with superparamagnetic iron oxide nanoparticles (SPIONs) into poly(acrylamide-co-acrylonitrile) microparticles via spray drying. The SPIONs are able to act as MRI contrast agents, thus resulting in potential theranostic formulations. Concave microparticles were observed by electron microscopy, and elemental mapping results suggest the LDH and SPION particles were homogeneously distributed inside the microparticles. In vitro dissolution tests showed that the drug was released over a prolonged period of time with the microspheres having distinct release curves at 37 and 43 °C, and the relaxivity (r2) profile microparticles were also found to be different over the temperature range 35 to 46 °C, both reflecting obvious thermo-responsive properties. Mathematical relationships between r2, release and temperature data were established, demonstrating that the microparticles have the potential for use in MRI-guided therapy. In vitro cell experiments revealed that the formulations permit synergistic hyperthermia-aided chemotherapy in cultured Caco-2 and A549 cells. Thus, the microparticles prepared in this work have potential as smart stimuli-responsive theranostics for hyperthermia-aided chemotherapy

Layer-by-Layer Self-Assembly: Toward Magnetic Films with Tunable Anisotropy

Highly anisotropic magnetic films are possible to fabricate by control of the coupling between individual magnetic particles. Selective control over coupling in the horizontal and vertical directions are of both fundamental and practical interest. Here we show such control in the multiple layer-by-layer (LBL) self-assembly of layered double hydroxide (LDH) nanosheets (<i>x</i> = 1, 2, 3 and 4) with thicknesses of 5–15 nm, co-assembled with 3-aminopropyl-trimethoxysilane (APTS) modified spherical Fe₃O₄ nanoparticles (APTS-Fe₃O₄ NPs) on quartz substrates. The electrostatic charge density on the LDH sheets, controlled by the Mg/Al composition ratio, affects the NP packing in a single horizontal layer, while the thickness of the LDH sheets controls magnetic coupling between layers. The tunable magnetic properties (coercivity <i>H</i>_c, saturation magnetization <i>M</i>_s, anisotropy, and blocking temperatures) are measured as a function of these parameters. The maximum saturation magnetizations <i>M</i>_s, 36.3 and 25.1 emu·g^–1 in the perpendicular and parallel direction, respectively, are found for the sample of <i>x</i> = 3 = Mg/Al ratio in the LDH layer, and 15 nm LDH layer thickness. This work provides a general method to adjust the anisotropy of magnetic films based on directional control of coupling of magnetic nanoparticles between and across, LDH nanosheets. We outline how higher anisotropy and even finer control could be achieved by pH and composition control over the electrostatic charge of the assembly components