Cerium oxide nanoparticles in neuroprotection and considerations for efficacy and safety

Rzigalinski, Beverly A.; Carfagna, Charles S.; Ehrich, Marion

doi:10.1002/wnan.1444

Cited by 110 publications

(77 citation statements)

References 89 publications

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“…Among the biological effects of nanoceria, their neuroprotection capability is particular intriguing . For instance, Lee et al found that cerium oxide nanoparticles can induce changes in the murine neuronal cell transcriptome with a particular involvement of genes related to neurological disease, cell cycle control, and growth .…”

Section: Redox‐active Nanoparticlessupporting

confidence: 63%

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Remote Control of Cellular Functions: The Role of Smart Nanomaterials in the Medicine of the Future

Genchi

Marino

Grillone

et al. 2017

Adv Healthcare Materials

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The remote control of cellular functions through smart nanomaterials represents a biomanipulation approach with unprecedented potential applications in many fields of medicine, ranging from cancer therapy to tissue engineering. By actively responding to external stimuli, smart nanomaterials act as real nanotransducers able to mediate and/or convert different forms of energy into both physical and chemical cues, fostering specific cell behaviors. This report describes those classes of nanomaterials that have mostly paved the way to a "wireless" control of biological phenomena, focusing the discussion on some examples close to the clinical practice. In particular, magnetic fields, light irradiation, ultrasound, and pH will be presented as means to manipulate the cellular fate, due to the peculiar physical/chemical properties of some smart nanoparticles, thus providing realistic examples of "nanorobots" approaching the visionary ideas of Richard Feynman.

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Section: Redox‐active Nanoparticlessupporting

confidence: 63%

“…Nanoceria antioxidant and regenerating mechanism based on sequential SOD‐ and CAT‐like reactions. Adapted with permission …”

Section: Redox‐active Nanoparticlesmentioning

confidence: 99%

Remote Control of Cellular Functions: The Role of Smart Nanomaterials in the Medicine of the Future

Genchi

Marino

Grillone

et al. 2017

Adv Healthcare Materials

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“…The degradation of the nanocomposite scaffold raises the question of the distribution of the CNPs throughout the body. Biodistribution studies completed in mice reported that CNPs do not cause an immunogenic response in the body (Hirst et al, ; Rajeshkumar & Naik, ; Rzigalinski, Carfagna, & Ehrich, ). Hirst et al () examined the accumulation of CNPs in the major organs of a rat: liver, spleen, lungs, kidney, heart, and brain.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo biocompatibility assessment of free radical scavenging nanocomposite scaffolds for bone tissue regeneration

Dulany

Hepburn

Goins

et al. 2019

J Biomedical Materials Res

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Bone is the second most transplanted tissue in the world, resulting in increased demand for bone grafts leading to the fabrication of synthetic scaffold grafting alternatives. Fracture sites are under increased oxidative stress after injuries, affecting osteoblast function and hindering fracture healing and remodeling. To counter oxidative stress, free radical scavenging agents, such as cerium oxide nanoparticles, have gained traction in tissue engineering. Toward the goal of developing a functional synthetic system for bone tissue engineering, we characterized the biocompatibility of a porous, bioactive, free radical scavenging nanocomposite scaffold composed of poly (1,8 octanediol-co-citrate), beta-tricalcium phosphate, and cerium oxide nanoparticles. We studied cellular and tissue compatibility utilizing in vitro and in vivo models to assess nanocomposite interactions with both human osteoblast cells and rat subcutaneous tissue. We found the scaffolds were biocompatible in both models and supported cell attachment, proliferation, mineralization, and infiltration. Using hydrogen peroxide, we simulated oxidative stress to study the protective properties of the nanocomposite scaffolds via a reduction in cytotoxicity and recovered mineralization of osteoblast cells in vitro. We also found after implantation in vivo the scaffolds exhibited biocompatible properties essential for successful scaffolds for bone tissue engineering. Cells were able to infiltrate through the scaffolds, the surrounding tissues elicited a minimal immune response, and there were signs of scaffold degradation after 30 days of implantation.After the array of biological characterization, we had confirmed the development of a nanocomposite scaffold system capable of supporting bone-remodeling processes while providing a protective free radical scavenging effect. K E Y W O R D S biocompatibility, cerium, free radical scavenging, human osteoblasts, nanocomposite scaffolds, subcutaneous implant

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“…3c), LR CNPs may have exerted their ROS scavenging effect by enhancing the cellular antioxidant enzyme activities as means of maintaining redox balance. CNPs are known for their broad spectrum antioxidant mechanisms 28,29 ; however, to the best our knowledge, the ability of CNPs to enhance cellular antioxidant enzyme activity in vitro has not been demonstrated. Due to limited studies in the field, the exact antioxidant mechanisms (scavenging of radicals, superoxides or peroxides) required for inhibiting valve calcification remain elusive.…”

Section: Resultsmentioning

confidence: 96%

Shape-Specific Nanoceria Mitigate Oxidative Stress-Induced Calcification in Primary Human Valvular Interstitial Cell Culture

et al. 2017

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Introduction Lack of effective pharmacological treatment makes valvular calcification a significant clinical problem in patients with valvular disease and bioprosthetic/mechanical valve replacement therapies. Elevated levels of reactive oxygen species (ROS) in valve tissue have been identified as a prominent hallmark and driving factor for valvular calcification. However, the therapeutic value of ROS-modulating agents for valvular calcification remains elusive. We hypothesized that ROS-modulating shape-specific cerium oxide nanoparticles (CNPs) will inhibit oxidative stress-induced valvular calcification. CNPs are a class of self-regenerative ROS-modulating agents, which can switch between Ce3+ and Ce4+ in response to oxidative microen-vironment. In this work, we developed oxidative stress-induced valve calcification model using two patient-derived stenotic valve interstitial cells (hVICs) and investigated the therapeutic effect of shape-specific CNPs to inhibit hVIC calcification. Methods Human valvular interstitial cells (hVICs) were obtained from a normal healthy donor and two patients with calcified aortic valves. hVICs were characterized for their phenotypic (mesenchymal, myofibroblast and osteoblast) marker expression by qRT-PCR and antioxidant enzymes activity before and after exposure to hydrogen peroxide (H2O2)-induced oxidative stress. Four shape-specific CNPs (sphere, short rod, long rod, and cube) were synthesized via hydrothermal or ultra-sonication method and characterized for their biocompatibility in hVICs by alamarBlue® assay, and ROS scavenging ability by DCFH-DA assay. H2O2 and inorganic phosphate (Pi) were co-administrated to induce hVIC calcification in vitro as demonstrated by Alizarin Red S staining and calcium quantification. The effect of CNPs on inhibiting H2O2-induced hVIC calcification was evaluated. Results hVICs isolated from calcified valves exhibited elevated osteoblast marker expression and decreased antioxidant enzyme activities compared to the normal hVICs. Due to the impaired antioxidant enzyme activities, acute H2O2-induced oxidative stress resulted in higher ROS levels and osteoblast marker expression in both diseased hVICs when compared to the normal hVICs. Shape-specific CNPs exhibited shape-dependent abiotic ROS scavenging ability, and excellent cytocompatibility. Rod and sphere CNPs scavenged H2O2-induced oxidative stress in hVICs in a shape- and dose-dependent manner by lowering intracellular ROS levels and osteoblast marker expression. Further, CNPs also enhanced activity of antioxidant enzymes in hVICs to combat oxidative stress. Cube CNPs were not effective ROS scavengers. The addition of H2O2 in the Pi-induced calcification model further increased calcium deposition in vitro in a time-dependent manner. Co-administration of rod CNPs with Pi and H2O2 mitigated calcification in the diseased hVICs. Conclusions We demonstrated that hVICs derived from calcified valves exhibited impaired antioxidant defense mechanisms and were more susceptible to oxidative stress th...

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Cerium oxide nanoparticles in neuroprotection and considerations for efficacy and safety

Cited by 110 publications

References 89 publications

Remote Control of Cellular Functions: The Role of Smart Nanomaterials in the Medicine of the Future

Remote Control of Cellular Functions: The Role of Smart Nanomaterials in the Medicine of the Future

In vitro and in vivo biocompatibility assessment of free radical scavenging nanocomposite scaffolds for bone tissue regeneration

Shape-Specific Nanoceria Mitigate Oxidative Stress-Induced Calcification in Primary Human Valvular Interstitial Cell Culture

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