Ceria Nanoparticles Meet Hepatic Ischemia‐Reperfusion Injury: The Perfect Imperfection

Ni, Dalong; Wu, Hao; Chen, Wei-Yu; Bao, Qunqun; Rosenkrans, Zachary T.; Barnhart, Todd E.; Ferreira, Carolina A.; Wang, Yiguang; Yao, Heliang; Sun, Tuanwei; Jiang, Dawei; Li, Shiyong; Cao, Tianye; Liu, Zhaofei; Engle, Jonathan W.; Hu, Ping; Lan, Xiaoli; Cai, Weibo

doi:10.1002/adma.201902956

Cited by 181 publications

(184 citation statements)

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“…First, because it is the organ where the majority of the administered nanomaterials passively accumulate. Thus, it represents a major testing field to start the studies of the NPs evolution, pharmacokinetics, and activity, [ 42 ] and consequently, enable the clinical translation of newly developed nanomedicines. Second, the liver is where many discrepant reports show protective effects of CeO 2 NPs against ROS overproduction and inflammatory processes or the opposite, a role in promoting oxidative stress and toxicity (Section 3).…”

Section: Introductionmentioning

confidence: 99%

Cerium Oxide Nanoparticles: Advances in Biodistribution, Toxicity, and Preclinical Exploration

Casals

Zeng

Parra‐Robert

et al. 2020

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116

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to contribute to improved treatments by the generation of new diagnostic and therapeutic products. In particular, inorganic nanoparticles (NPs) have emerged as flexible platforms to develop new imaging and therapy agents for detecting and treating diseases at its earliest stages, with benefits superior to any currently used treatments. [1] These materials have been reported as robust drug carriers, versatile scaffolds able to adjust conjugated biomolecules activity, and antennas that can be excited in biologically transparent media. [2] Besides, they can be easily detected and tracked in physiological environments due to their unique physicochemical signatures. [3] Thus, nowadays, with the requirements for more personalized treatments and precision medications, [4] the interest in these materials to develop multimodal/multifunctional nanosized particles that can perform diagnosis [5] and different therapies (such as chemo-, thermo-, radio-, immunotherapies) in a single nanoplatform [6] is continuously growing. [7] Among the broad range of newly proposed nanomaterials, antioxidant NPs add to this list of advantages that they even Antioxidant nanoparticles have recently gained tremendous attention for their enormous potential in biomedicine. However, discrepant reports of either medical benefits or toxicity, and lack of reproducibility of many studies, generate uncertainties delaying their effective implementation. Herein, the case of cerium oxide is considered, a well-known catalyst in the petrochemistry industry and one of the first antioxidant nanoparticles proposed for medicine. Like other nanoparticles, it is now described as a promising therapeutic alternative, now as threatening to health. Sources of these discrepancies and how this analysis helps to overcome contradictions found for other nanoparticles are summarized and discussed. For the context of this analysis, what has been reported in the liver is reviewed, where many diseases are related to oxidative stress. Since well-dispersed nanoparticles passively accumulate in liver, it represents a major testing field for the study of new nanomedicines and their clinical translation. Even more, many contradictory works have reported in liver either cerium-oxide-associated toxicity or protection against oxidative stress and inflammation. Based on this, finally, the intention is to propose solutions to design improved nanoparticles that will work more precisely in medicine and safely in society.

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Section: Introductionmentioning

confidence: 99%

Cerium Oxide Nanoparticles: Advances in Biodistribution, Toxicity, and Preclinical Exploration

Casals

Zeng

Parra‐Robert

et al. 2020

Small

116

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“…The plausible mechanism could be that controlled reactive oxygen species generation and consequently reduced redox signaling (Nethi et al, 2014). A similar mechanism was proven in the treatment of hepatic ischemia-reperfusion using ceria NPs (Ni et al, 2019). Later, another study indicated that VEGF on fibronectin-incorporated AuNPs promoted MSCs migration through the endothelial oxide synthase/metalloproteinase signaling pathway, which promoted MSC proliferation and increased the biocompatibility of the particle (Chen et al, 2018).…”

Section: Nps' Application In Peripheral Vascular Regenerationmentioning

confidence: 75%

The Roles of Nanoparticles in Stem Cell-Based Therapy for Cardiovascular Disease

Sun

et al. 2020

Front. Bioeng. Biotechnol.

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Cardiovascular disease (CVD) is currently one of the primary causes of mortality and morbidity worldwide. Nanoparticles (NPs) are playing increasingly important roles in regulating stem cell behavior because of their special features, including shape, size, aspect ratio, surface charge, and surface area. In terms of cardiac disease, NPs can facilitate gene delivery in stem cells, track the stem cells in vivo for long-term monitoring, and enhance retention after their transplantation. The advantages of applying NPs in peripheral vascular disease treatments include facilitating stem cell therapy, mimicking the extracellular matrix environment, and utilizing a safe non-viral gene delivery tool. However, the main limitation of NPs is toxicity, which is related to their size, shape, aspect ratio, and surface charge. Currently, there have been many animal models proving NPs' potential in treating CVD, but no extensive applications of stem-cell therapy using NPs are available in clinical practice. In conclusion, NPs might have significant potential uses in clinical trials of CVD in the future, thereby meeting the changing needs of individual patients worldwide.

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“…Recently, nanomaterials with enzyme-like activity named nanozymes, 21,22 have been exploited as potential therapeutics in various diseases, including Parkinson's disease, 23 Alzheimer's disease, 24 cancer, [25][26][27] ischemic stroke, 28,29 and ischemia reperfusion injury, 30 through mainly eliminating ROS levels in cells. For instance, Mn 3 O 4 nanozymes have been used as a promising therapeutic agent for treating inflammation because of their excellent ROS scavenging activity.…”

Section: Introductionmentioning

confidence: 99%

<p>Cyclodextrin-Modified CeO<sub>2</sub> Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis</p>

Wu¹,

Liu²,

Wang³

et al. 2020

IJN

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Reactive oxygen species (ROS)-induced oxidative stress plays a key role in the pathogenesis and progression of psoriasis by causing inflammation. Antioxidative strategies eradicating ROS may serve as effective and easy treatment options for psoriasis, while nanozymes with intrinsic antioxidant enzyme-like activity have not been explored for psoriasis treatment. The aim of this study is to fabricate β-cyclodextrins (β-CDs)-modified ceria nanoparticles (β-CDs/CeO 2 NPs) with drug-loaded and multimimic-enzyme activities for combinational psoriasis therapy. Methods: The β-CDs/CeO 2 NPs were synthesized by a hydrothermal method using unmodified β-CDs as a protecting agent. The structure, size and morphology were analyzed by dynamic light scattering, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and Fourier transform infrared (FTIR) spectroscopy. Considering the superoxide dismutase (SOD)-and catalase-mimetic activities, the in vitro antioxidant activity of the β-CDs/CeO2 NPs was investigated. After dithranol (DIT) was loaded, the drug-loading capacity and release profile were determined by UV-visible light spectrophotometer and high-performance liquid chromatography. The anti-psoriatic efficacy was studied in the imiquimod (IMQ)-induced mouse model on the basis of morphological evaluation, psoriasis area and severity index calculation (PASI), and inflammatory cytokine expression. Results: The average particle size of the blank β-CDs/CeO 2 NPs was 60.89±0.32 nm with a polydispersity index (PDI) of 0.12, whereas that of the DIT-loaded NPs was 79.38±1.06 nm with a PDI of 0.27. TEM results showed the as-prepared NPs formed a uniform quasispherical shape with low polydispersity. XPS indicates synthesized NPs have a mixed Ce 3 + /Ce 4+ valence state. FTIR spectroscopy confirmed the presence of β-CDs and DIT in the NPs. Inhibition of superoxide anion rate by NPs could be reached to 79.4% in the presence of 200 µg/mL, and elimination of H 2 O 2 efficiency reached about 50% in the presence of 40 µg/ mL, demonstrating excellent superoxide dismutase-and catalase-mimicking activities, thereby providing remarkable cryoprotection against ROS-mediated damage. Furthermore, β-CDs on the surface endowed the NPs with drug-loading function via host-guest interactions. The entrapment efficiency and drug loading of DIT are 94.7% and 3.48%, respectively. The in vitro drug release curves revealed a suitable release capability of DIT@β-CDs/CeO 2 NPs under physiological conditions. In IMQ-induced psoriatic model, the DIT@β-CDs/CeO 2 NPs exhibited excellent therapeutic effect. Conclusion: This study may pave the way for the application of nanozyme β-CDs/CeO 2 NPs as a powerful tool for psoriasis therapy.

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Ceria Nanoparticles Meet Hepatic Ischemia‐Reperfusion Injury: The Perfect Imperfection

Cited by 181 publications

References 50 publications

Cerium Oxide Nanoparticles: Advances in Biodistribution, Toxicity, and Preclinical Exploration

Cerium Oxide Nanoparticles: Advances in Biodistribution, Toxicity, and Preclinical Exploration

The Roles of Nanoparticles in Stem Cell-Based Therapy for Cardiovascular Disease

<p>Cyclodextrin-Modified CeO<sub>2</sub> Nanoparticles as a Multifunctional Nanozyme for Combinational Therapy of Psoriasis</p>

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