Influence of Eu3+ Doping on Physiochemical Properties and Neuroprotective Potential of Polyacrylic Acid Functionalized Cerium Oxide Nanoparticles.

Cerium oxide nanoparticles (CeONPs) exhibiting antioxidant properties are investigated as potential tools for neurodegenerative diseases. Here, we synthesized polyacrylic acid conjugated cerium oxide (CeO) nanoparticles, and further to enhance their neuroprotective effect, Eu3+ was substituted at different concentrations (5, 10, 15 and 20 mol%) to the CeO, which can also impart fluorescence to the system. CeONPs and Eu-CeONPs in the size range of 15-30 nm were stable at room temperature. The X-ray Photoelectron Spectroscopy (XPS) analysis revealed the chemical state of Eu and Ce components, and we could conclude that all Eu3+ detected on the surface is well integrated into the cerium oxide lattice. The emission spectrum of Eu-CeO arising from the 7F0 → 5D1 MD and 7F0 → 5D2 transitions indicated the Eu3+ ion acting as a luminescence center. The fluorescence of Eu-CeONPs was visualized by depositing them at the surface of positively charged latex particles. The developed nanoparticles were safe for human neuronal-like cells. Compared with CeONPs, Eu-CeONPs at all concentrations exhibited enhanced neuroprotection against 6-OHDA, while the protection trend of Eu-CeO was similar to that of CeO against H2O2 in SH-SY5Y cells. Hence, the developed Eu-CeONPs could be further investigated as a potential theranostic probe.

Neuroprotective effects of polyacrylic acid (PAA) conjugated cerium oxide against hydrogen peroxide- and 6-OHDA-induced SH-SY5Y cell damage.

Cerium oxide nanoparticles have been widely investigated against neurodegenerative diseases due to their antioxidant properties that aid in quenching reactive oxygen species. In this study, polyacrylic acid conjugated cerium oxide (PAA-CeO) nanoparticles were synthesized in a 50-60 nm size range with a zeta potential of - 35 mV. X-ray photoelectron spectroscopy analysis revealed a mixed valence state of Ce4+ and Ce3+. PAA-CeO nanoparticles were safe for undifferentiated (UN-) and retinoic acid-differentiated (RA-) human neuroblastoma SH-SY5Y cells and reduced the extent of cell damage evoked by hydrogen peroxide (H2O2) and 6-hydroxydopamine (6-OHDA). In the H2O2 model of cell damage PAA-CeO did not affect the caspase-3 activity (apoptosis marker) but attenuated the number of propidium iodide-positive cells (necrosis marker). In the 6-OHDA model, nanoparticles profoundly reduced necrotic changes and partially attenuated caspase-3 activity. However, we did not observe any impact of PAA-CeO on intracellular ROS formation induced by H2O2. Further, the flow cytometry analysis of fluorescein isothiocyanate-labeled PAA-CeO revealed a time- and concentration-dependent cellular uptake of nanoparticles. The results point to the neuroprotective potential of PAA-CeO nanoparticles against neuronal cell damage induced by H2O2 and 6-OHDA, which are in both models associated with the inhibition of necrotic processes and the model-dependent attenuation of activity of executor apoptotic protease, caspase-3 (6-OHDA model) but not with the direct inhibition of ROS (H2O2 model).

Nanocarriers for effective nutraceutical delivery to the brain.

Neurodegenerative disorders are common among aging populations around the globe. Most are characterized by loss of neurons, protein aggregates, oxidative stress, mitochondrial damage, neuroinflammation among others. Although symptomatic treatment using conventional pharmacotherapy has been widely employed, their therapeutic success is limited due to varied reasons. In the need to identify an alternative approach, researchers successfully demonstrated the therapeutic utility of plant-derived nutraceuticals in cell and animal models of neurodegenerative conditions. However, most nutraceuticals failed during clinical trials in humans owing to their poor bioavailability in vivo and limited permeability across the blood brain barrier (BBB). The current emphasis is therefore on the improved delivery of nutraceuticals to the brain. In this regard, development of nanoparticle conjugated nutraceuticals to enhance bioavailability and therapeutic efficacy in the brain has gained attention. Here, we review the research advances in nanoparticles conjugated nutraceuticals applied in neurodegenerative disorders and discuss their advantages and limitations, clinical trials and toxicity concerns.

Unveiling the Effects of Rare-Earth Substitutions on the Structure, Mechanical, Optical, and Imaging Features of ZrO2 for Biomedical Applications.

The impact of selective rare-earth (RE) additions in ZrO2-based ceramics on the resultant crystal structure, mechanical, morphological, optical, magnetic, and imaging contrast features for potential applications in biomedicine is explored. Six different RE, namely, Yb3+, Dy3+, Tb3+, Gd3+, Eu3+, and Nd3+ alongside their variations in the dopant concentrations were selected to accomplish a wide range of combinations. The experimental observations affirmed the roles of size and dopant concentration in determining the crystalline phase behavior of ZrO2. The significance of tetragonal ZrO2 (t-ZrO2) → monoclinic ZrO2 degradation is evident with 10 mol % of RE substitution, while RE contents in the range of 20 and 40 mol % ensured either t-ZrO2 or cubic ZrO2 (c-ZrO2) stability until 1500 °C. High RE content in the range of 80-100 mol % still confirmed the structural stability of c-ZrO2 for lower-sized Yb3+, Dy3+, and Tb3+, while the c-ZrO2 → RE2Zr2O7 phase transition becomes evident for higher-sized Gd3+, Eu3+, and Nd3+. A steady decline in the mechanical properties alongside a quenching effect experienced in the emission phenomena is apparent for high RE concentrations in ZrO2. On the one hand, the paramagnetic characteristics of Dy3+, Tb3+, Gd3+, and Nd3+ fetched excellent contrast features from magnetic resonance imaging analysis. On the other hand, Yb3+ and Dy3+ added systems exhibited good X-ray absorption coefficient values determined from computed tomography analysis.

Lanthanide phosphate (LnPO4 ) rods as bio-probes: A systematic investigation on structural, optical, magnetic, and biological characteristics.

The proposed work involves an exclusive study on the synthesis protocol, crystal structure analysis, and imaging contrast features of unique lanthanide phosphates (LnPO4 ). XRD and Raman spectra affirmed the ability of the proposed synthesis technique to achieve unique LnPO4 devoid of impurities. The crystal structure analysis confirms the P121/c1 space setting of NdPO4 , EuPO4 , GdPO4 , and TbPO4 that all uniformly crystallizes in monoclinic unit cell. In a similar manner, the tetragonal crystal setting of DyPO4 , ErPO4 , HoPO4 , and YbPO4 that unvaryingly possess the I41/amd space setting is confirmed. Under the same synthesis conditions, the monoclinic (Eu) and tetragonal (Ho) lanthanide phosphates displayed uniform rod-like morphologies. Absorption and luminescence properties of unique LnPO4 were determined. In vitro biological studies demonstrated low toxicity levels of LnPO4 and clearly distinguished fluorescence of TbPO4 and EuPO4 in Y79, retinoblastoma cell lines. The paramagnetic response of GdPO4 , NdPO4 , DyPO4 , TbPO4 , and HoPO4 facilitated excellent magnetic resonance imaging (MRI) contrast features. Meanwhile, GdPO4 , DyPO4 , HoPO4 , and YbPO4 possessing higher X-ray absorption coefficient than clinical contrast Omnipaque™ exhibited high computed tomography (CT) efficiency. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 1372-1383, 2019.

Design and structural investigations of Yb3+ substituted ß-Ca3(PO4)2 contrast agents for bimodal NIR luminescence and X-ray CT imaging.

The quest for the development of bone substitutes with contrast agents for diagnostic imaging subsists to distinguish synthetic bone from native human tissue. To this aim, ytterbium (Yb3+) substitutions in ß-tricalcium phosphate (ß-Ca3(PO4)2, ß-TCP) as contrast agents has been developed to differentiate implant materials thereby, facilitating as host for bimodal imaging application by means of NIR luminescence and X-ray computed tomography techniques. A facile aqueous chemical precipitation route with the aid of surfactant is used for the synthesis of Yb3+ substitutions in ß-Ca3(PO4)2. The characterization results affirms the ability of ß-Ca3(PO4)2 to host 4.36 mol% of Yb3+ while the excess Yb3+ crystallizes as YbPO4. The structure refinement results favour the occupancy of Yb3+ at the Ca2+(5) site of ß-Ca3(PO4)2. The absorption and photoluminescence spectra in the near infrared region with emission intensity ~1024 nm in the second biological window correspond to 2F5/2 → 2F7/2 transitions of Yb3+. The designed Yb3+ substituted ß-Ca3(PO4)2 does not exhibit any toxicity in human osteosarcoma cell lines and delivers an excellent in vitro CT contrast ability allied by the enhanced signal intensity and high X-ray absorption coefficient.

Cosubstitution of Lanthanides (Gd3+/Dy3+/Yb3+) in ß-Ca3(PO4)2 for Upconversion Luminescence, CT/MRI Multimodal Imaging.

Multifunctional Gd3+, Dy3+ and Yb3+ cosubstitutions in ß-Ca3(PO4)2 were achieved through a facile synthetic technique. Gd3+ and Dy3+ prefer to occupy the 7-fold coordinated Ca2+(1), 6- or 8-fold coordinated Ca2+(2), and 8-fold coordinated Ca2+(3) sites of the ß-Ca3(PO4)2 structure. The shortest Ca(5)-O bond length of te Ca2+(5) site with 6-fold co-ordination favors Yb3+ accommodation. The substitution limit of each dopant to attain ß-Ca3(PO4)2 solid solution is determined as ∼1.25 mol %. The combined substitutions displayed upconversion emission in blue, yellow and red regions on excitation at 980 nm via the energy transfer mechanism from Yb3+ to Dy3+. Yb3+ and Dy3+ combination induces a high X-ray absorption ability for computed tomography (CT). The materials also displayed paramagnetic behavior and exhibited high longitudinal (r1 = 48.71 mM-1 s-1) and transverse relaxivity (r2 = 61.79 mM-1 s-1) indicating their potential as T1 and T2 contrast agents in magnetic resonance imaging (MRI). The negligible toxicity of Gd3+/Dy3+/Yb3+ cosubstitutions in ß-Ca3(PO4)2 is also demonstrated. The overall results justify the potential of the developed material as possible contrast agent for T1 and T2 MRI/CT/upconversion luminescence.

Substitutional limit of gadolinium in ß-tricalcium phosphate and its magnetic resonance imaging characteristics.

To compensate the limitations of bone tissue magnetic resonance imaging (MRI), a series of gadolinium (Gd3+ ) substituted ß-Tricalcium phosphate [ß-TCP, ß-Ca3 (PO4 )2 ] were developed. All the powders were characterized using XRD, Raman spectroscopy, Rietveld refinement of the XRD data and the studies confirmed the Gd3+ occupancy at Ca2+ (1), Ca2+ (2) and Ca2+ (3) lattice sites of ß-Ca3 (PO4 )2. HR-TEM analysis revealed the spherical nature of particles with diameter about 100 nm. The Gd3+ doped ß-Ca3 (PO4 )2 exhibited non-toxic behaviour to MG-63 cells in vitro and the room temperature magnetic field versus magnetization measurements confirmed its paramagnetic behaviour. MRI analysis revelas that it shorten both T1 and T2 proton relaxation times, thus influencing both r1 and r2 relaxivity values that reach 61.97 mM-1 s-1 and 73.35 mM-1 s-1 . © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2545-2552, 2017.

Synthesis, structure, thermal stability, mechanical and antibacterial behaviour of lanthanum (La³âº) substitutions in ß-tricalciumphosphate.

Five different concentrations of lanthanum (La(3+)) substituted ß-tricalcium phosphate [ß-TCP, ß-Ca3(PO4)2] were formed through aqueous precipitation technique and the results were compared with stoichiometric ß-TCP. All the La(3+) substituted ß-TCP powders were characterized using XRD, FT-IR, XRF, Raman spectroscopy and Rietveld refinement of the XRD data. The results from the investigation confirmed the presence of La(3+) in rhombohedral ß-TCP structure. The substitution of higher sized of La(3+) led to the considerable enhancement in lattice parameters of ß-TCP crystal structure and La(3+) was found to have occupied the eight fold coordinated Ca (3) site of ß-TCP structure. La(3+) occupancy at the Ca (3) site resulted in the significant distortions of the associated PO4 tetrahedra, which were supported by the Raman and FT-IR spectroscopic techniques. La(3+) presence in the crystal lattice of ß-TCP also led to the delay in allotropic phase transformation of ß-TCP to α-TCP till 1300°C, thus signifying the good thermal stability of La(3+) substituted ß-TCP powders. The antibacterial efficiency of La(3+) substituted ß-TCP powders was confirmed from the in vitro tests done on microbes such as Staphylococcus aureus and Escheria coli. Further, the presence of La(3+) in the crystal lattice of ß-TCP did not affect the hardness and Young's modulus values of ß-TCP.