Authors: Yamei Liu, Shuya Wang, Jiaxiong Zhang...

Myocardial infarction (MI) has a 5-year mortality rate of more than 50% due to the lack of effective treatments. Interactions between cardiomyocytes and the MI microenvironment (MIM) can determine the progression and fate of infarcted myocardial tissue. Here, a specially designed Melanin-based composite nanomedicines (MCN) is developed to effectively treat MI by reprogramming the MIM. MCN is a nanocomposite composed of polydopamine (P), Prussian blue (PB) and cerium oxide (CeO) with a Mayuan-like structure, which reprogramming the MIM by the efficient conversion of detrimental substances (H, reactive oxygen species, and hypoxia) into beneficial status (O and HO). In coronary artery ligation and ischemia reperfusion models of male mice, intravenously injecting MCN specifically targets the damaged area, resulting in restoration of cardiac function. With its promising therapeutic effects, MCN constitutes a new agent for MI treatment and demonstrates potential for clinical application.

Topics: Animals; Melanins; Myocardial Infarction; Male; Mice; Nanomedicine; Indoles; Polymers; Cerium; Myocytes, Cardiac; Nanocomposites; Disease Models, Animal; Reactive Oxygen Species; Mice, Inbred C57BL; Cellular Microenvironment; Ferrocyanides

PubMed: 39103330
DOI: 10.1038/s41467-024-50854-4

Authors: Ilse Gosens, Jordi Minnema, A John F Boere...

BACKGROUND

Physiologically based kinetic models facilitate the safety assessment of inhaled engineered nanomaterials (ENMs). To develop these models, high quality datasets on well-characterized ENMs are needed. However, there are at present, several data gaps in the systemic availability of poorly soluble particles after inhalation. The aim of the present study was therefore to acquire two comparable datasets to parametrize a physiologically-based kinetic model.

METHOD

Rats were exposed to cerium dioxide (CeO, 28.4 ± 10.4 nm) and titanium dioxide (TiO 21.6 ± 1.5 nm) ENMs in a single nose-only exposure to 20 mg/m or a repeated exposure of 2 × 5 days to 5 mg/m. Different dose levels were obtained by varying the exposure time for 30 min, 2 or 6 h per day. The content of cerium or titanium in three compartments of the lung (tissue, epithelial lining fluid and freely moving cells), mediastinal lymph nodes, liver, spleen, kidney, blood and excreta was measured by Inductively Coupled Plasma-Mass Spectrometry (ICP-MS) at various time points post-exposure. As biodistribution is best studied at sub-toxic dose levels, lactate dehydrogenase (LDH), total protein, total cell numbers and differential cell counts were determined in bronchoalveolar lavage fluid (BALF).

RESULTS

Although similar lung deposited doses were obtained for both materials, exposure to CeO induced persistent inflammation indicated by neutrophil granulocytes influx and exhibited an increased lung elimination half-time, while exposure to TiO did not. The lavaged lung tissue contained the highest metal concentration compared to the lavage fluid and cells in the lavage fluid for both materials. Increased cerium concentrations above control levels in secondary organs such as lymph nodes, liver, spleen, kidney, urine and faeces were detected, while for titanium this was found in lymph nodes and liver after repeated exposure and in blood and faeces after a single exposure.

CONCLUSION

We have provided insight in the distribution kinetics of these two ENMs based on experimental data and modelling. The study design allows extrapolation at different dose-levels and study durations. Despite equal dose levels of both ENMs, we observed different distribution patterns, that, in part may be explained by subtle differences in biological responses in the lung.

Topics: Animals; Titanium; Cerium; Tissue Distribution; Inhalation Exposure; Male; Lung; Bronchoalveolar Lavage Fluid; Rats; Nanostructures; Administration, Inhalation; Rats, Wistar; Models, Biological; Particle Size; Metal Nanoparticles

PubMed: 39143599
DOI: 10.1186/s12989-024-00588-4

Review

Authors: Alfonso Zambon, Gianluca Malavasi, Annalisa Pallini...

Bioactive glasses (BGs) for biomedical applications are doped with therapeutic inorganic ions (TIIs) in order to improve their performance and reduce the side effects related to the surgical implant. Recent literature in the field shows a rekindled interest toward rare earth elements, in particular cerium, and their catalytic properties. Cerium-doped bioactive glasses (Ce-BGs) differ in compositions, synthetic methods, features, and assessment. This review provides an overview on the recent development of Ce-BGs for biomedical applications and on the evaluation of their bioactivity, cytocompatibility, antibacterial, antioxidant, and osteogenic and angiogenic properties as a function of their composition and physicochemical parameters.

Topics: Anti-Bacterial Agents; Catalysis; Cerium; Glass; Osteogenesis

PubMed: 34468119
DOI: 10.1021/acsbiomaterials.1c00414

Review

Authors: Beverly A Rzigalinski, Charles S Carfagna, Marion Ehrich...

Cerium oxide nanoparticles have widespread use in the materials industry, and have recently come into consideration for biomedical use due to their potent regenerative antioxidant properties. Given that the brain is one of the most highly oxidative organs in the body, it is subject to some of the greatest levels of oxidative stress, particularly in neurodegenerative disease. Therefore, cerium oxide nanoparticles are currently being investigated for efficacy in several neurodegenerative disorders and have shown promising levels of neuroprotection. This review discusses the basis for cerium oxide nanoparticle use in neurodegenerative disease and its hypothesized mechanism of action. The review focuses on an up-to-date summary of in vivo work with cerium oxide nanoparticles in animal models of neurodegenerative disease. Additionally, we examine the current state of information regarding biodistribution, toxicity, and safety for cerium oxide nanoparticles at the in vivo level. Finally, we discuss future directions that are necessary if this nanopharmaceutical is to move up from the bench to the bedside. WIREs Nanomed Nanobiotechnol 2017, 9:e1444. doi: 10.1002/wnan.1444 For further resources related to this article, please visit the WIREs website.

Topics: Animals; Antioxidants; Cerium; Humans; Nanoparticles; Neurodegenerative Diseases; Neuroprotection; Oxidative Stress; Tissue Distribution

PubMed: 27860449
DOI: 10.1002/wnan.1444

Review

Authors: Xiaoxuan Fu, Peng Li, Xi Chen...

Ceria nanoparticles (CeO NPs) have become popular materials in biomedical and industrial fields due to their potential applications in anti-oxidation, cancer therapy, photocatalytic degradation of pollutants, sensors, etc. Many methods, including gas phase, solid phase, liquid phase, and the newly proposed green synthesis method, have been reported for the synthesis of CeO NPs. Due to the wide application of CeO NPs, concerns about their adverse impacts on human health have been raised. This review covers recent studies on the biomedical applications of CeO NPs, including their use in the treatment of various diseases (e.‍g., Alzheimer's disease, ischemic stroke, retinal damage, chronic inflammation, and cancer). CeO NP toxicity is discussed in terms of the different systems of the human body (e.‍g., cytotoxicity, genotoxicity, respiratory toxicity, neurotoxicity, and hepatotoxicity). This comprehensive review covers both fundamental discoveries and exploratory progress in CeO NP research that may lead to practical developments in the future.

Topics: Cerium; Humans; Animals; Metal Nanoparticles; Neoplasms; Alzheimer Disease; Nanoparticles

PubMed: 38725338
DOI: 10.1631/jzus.B2300854

Authors: Xia Kang, Laszlo Csetenyi, Geoffrey Michael Gadd...

Cerium is the most sought-after rare earth element (REE) for application in high-tech electronic devices and versatile nanomaterials. In this research, biomass-free spent culture media of Aspergillus niger and Neurospora crassa containing precipitant ligands (oxalate, carbonate) were investigated for their potential application in biorecovery of Ce from solution. Precipitation occurred after Ce was mixed with biomass-free spent culture media and >99% Ce was recovered from media of both organisms. SEM showed that biogenic crystals with distinctive morphologies were formed in the biomass-free spent medium of A. niger. Irregularly-shaped nanoparticles with varying sizes ranging from 0.5 to 2 μm and amorphous biominerals were formed after mixing the carbonate-laden N. crassa supernatant, resulting from ureolysis of supplied urea, with Ce. Both biominerals contained Ce as the sole metal, and X-ray diffraction (XRD) and thermogravimetric analyses identified the biominerals resulting from the biomass-free A. niger and N. crassa spent media as cerium oxalate decahydrate [Ce(CO)·10HO] and cerium carbonate [Ce(CO)·8HO], respectively. Thermal decomposition experiments showed that the biogenic Ce oxalates and carbonates could be subsequently transformed into ceria (CeO). FTIR confirmed that both amorphous and nanoscale Ce carbonates contained carbonate (CO) groups. FTIR-multivariate analysis could classify the biominerals into three groups according to different Ce concentrations and showed that Ce carbonate biominerals of higher purity were produced when precipitated at higher Ce concentrations. This work provides new understanding of fungal biotransformations of soluble REE species and their biorecovery using biomass-free fungal culture systems and indicates the potential of using recovered REE as precursors for the biosynthesis of novel nanomaterials.

Topics: Cerium; Oxalates; Carbonates; Biotransformation; Culture Media

PubMed: 37495308
DOI: 10.1016/j.funbio.2022.07.006

Authors: Nikolay Petkov, Ivayla Pantcheva, Anela Ivanova...

The largely uncharted complexation chemistry of the veterinary polyether ionophores, monensic and salinomycinic acids (HL) with metal ions of type M and the known antiproliferative potential of antibiotics has provoked our interest in exploring the coordination processes between MonH/SalH and ions of Ce. (1) Methods: Novel monensinate and salinomycinate cerium(IV)-based complexes were synthesized and structurally characterized by elemental analysis, a plethora of physicochemical methods, density functional theory, molecular dynamics, and biological assays. (2) Results: The formation of coordination species of a general composition [CeL(OH)] and [CeL(NO)(OH)], depending on reaction conditions, was proven both experimentally and theoretically. The metal(IV) complexes [CeL(NO)(OH)] possess promising cytotoxic activity against the human tumor uterine cervix (HeLa) cell line, being highly selective (non-tumor embryo Lep-3 vs. HeLa) compared to cisplatin, oxaliplatin, and epirubicin.

Topics: Humans; Monensin; Cerium; Ionophores; Ions

PubMed: 37375231
DOI: 10.3390/molecules28124676

Review

Authors: Fahimeh Charbgoo, Mansor Bin Ahmad, Majid Darroudi...

CeO nanoparticles (NPs) have shown promising approaches as therapeutic agents in biology and medical sciences. The physicochemical properties of CeO-NPs, such as size, agglomeration status in liquid, and surface charge, play important roles in the ultimate interactions of the NP with target cells. Recently, CeO-NPs have been synthesized through several bio-directed methods applying natural and organic matrices as stabilizing agents in order to prepare biocompatible CeO-NPs, thereby solving the challenges regarding safety, and providing the appropriate situation for their effective use in biomedicine. This review discusses the different green strategies for CeO-NPs synthesis, their advantages and challenges that are to be overcome. In addition, this review focuses on recent progress in the potential application of CeO-NPs in biological and medical fields. Exploiting biocompatible CeO-NPs may improve outcomes profoundly with the promise of effective neurodegenerative therapy and multiple applications in nanobiotechnology.

Topics: Biopolymers; Biosensing Techniques; Cerium; Enzymes; Green Chemistry Technology; Nanoparticles

PubMed: 28260887
DOI: 10.2147/IJN.S124855

Authors: Rui Xiao, Jia Liu, Lin Shi...

BACKGROUND

Despite recent advances the prognosis of pulmonary hypertension remains poor and warrants novel therapeutic options. Extensive studies, including ours, have revealed that hypoxia-induced pulmonary hypertension is associated with high oxidative stress. Cerium oxide nanozyme or nanoparticles (CeNPs) have displayed catalytic activity mimicking both catalase and superoxide dismutase functions and have been widely used as an anti-oxidative stress approach. However, whether CeNPs can attenuate hypoxia-induced pulmonary vascular oxidative stress and pulmonary hypertension is unknown.

RESULTS

In this study, we designed a new ceria nanozyme or nanoparticle (AuCeNPs) exhibiting enhanced enzyme activity. The AuCeNPs significantly blunted the increase of reactive oxygen species and intracellular calcium concentration while limiting proliferation of pulmonary artery smooth muscle cells and pulmonary vasoconstriction in a model of hypoxia-induced pulmonary hypertension. In addition, the inhalation of nebulized AuCeNPs, but not CeNPs, not only prevented but also blunted hypoxia-induced pulmonary hypertension in rats. The benefits of AuCeNPs were associated with limited increase of intracellular calcium concentration as well as enhancement of extracellular calcium-sensing receptor (CaSR) activity and expression in rat pulmonary artery smooth muscle cells. Nebulised AuCeNPs showed a favorable safety profile, systemic arterial pressure, liver and kidney function, plasma Ca level, and blood biochemical parameters were not affected.

CONCLUSION

We conclude that AuCeNPs is an improved reactive oxygen species scavenger that effectively prevents and treats hypoxia-induced pulmonary hypertension.

Topics: Animals; Cerium; Rats; Hypertension, Pulmonary; Hypoxia; Reactive Oxygen Species; Male; Myocytes, Smooth Muscle; Pulmonary Artery; Rats, Sprague-Dawley; Oxidative Stress; Nanoparticles; Calcium

PubMed: 39160624
DOI: 10.1186/s12951-024-02738-4

Authors: Cristina Chircov, Maria-Andreea Mincă, Andreea Bianca Serban...

Numerous studies have reported the possibility of enhancing the properties of materials by incorporating foreign elements within their crystal lattice. In this context, while magnetite has widely known properties that have been used for various biomedical applications, the introduction of other metals within its structure could prospectively enhance its effectiveness. Specifically, zinc and cerium have demonstrated their biomedical potential through significant antioxidant, anticancer, and antimicrobial features. Therefore, the aim of the present study was to develop a series of zinc and/or cerium-substituted magnetite nanoparticles that could further be used in the medical sector. The nanostructures were synthesized through the co-precipitation method and their morpho-structural characteristics were evaluated through X-ray diffraction (XRD), inductively coupled plasma mass spectrometry (ICP-MS), X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), zeta potential, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX) analyses. Furthermore, the nanostructures were subjected to a ROS-Glo HO assay for assessing their antioxidant potential, MTT assay for determining their anticancer effects, and antimicrobial testing against , , and strains. Results have proven promising for future biomedical applications, as the nanostructures inhibit oxidative stress in normal cells, with between two- and three-fold reduction and cell proliferation in tumor cells; a two-fold decrease in cell viability and microbial growth; an inhibition zone diameter of 4-6 mm and minimum inhibitory concentration (MIC) of 1-2 mg/mL.

Topics: Zinc; Metal Nanoparticles; Staphylococcus aureus; Antioxidants; Hydrogen Peroxide; Cerium; Magnetite Nanoparticles; Anti-Infective Agents; X-Ray Diffraction; Microbial Sensitivity Tests; Anti-Bacterial Agents

PubMed: 37047223
DOI: 10.3390/ijms24076249