Ultrasmall platinum nanozymes as broad-spectrum antioxidants for theranostic application in acute kidney injury

Zhang, Dongyang; Liu, Hengke; Younis, Muhammad Rizwan; Shan, Lei; Yang, Chen; Lin, Jing; Qu, Junle; Huang, Peng

doi:10.1016/j.cej.2020.127371

Cited by 44 publications

(25 citation statements)

References 39 publications

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“…The recorded catalytic activities are comparable or better when compared to other CeONP formulations that showed efficacy in reducing hepatic ischemia 25 and acute kidney injury. 27 3.4. In Vitro ROS Scavenging Activities.…”

Section: Resultsmentioning

confidence: 99%

“…CeONP’s strong catalytic activity through the redox reaction has already been well-recognized and widely applied in petrochemical and materials industry. − More recently, CeONP have been increasingly investigated for the treatment of ROS-related diseases, including neurodegenerative diseases, , autoimmune diseases, ocular surface diseases, and ischemic and acute injuries. − Potential biomedical applications of CeONP are favorable since their ROS scavenging mechanism is analogous to biological processes that are used by endogenous enzymes in our body, such as superoxide dismutase (SOD) and catalase. − By designing our CeONP formulation to be ultrasmall, we further improved its feasibility in biomedical uses. Small hydrodynamic sizes of CeONP improve the chance of eventual clinical translation by promoting efficient renal clearance and thereby addresses toxicity concerns that arise from long-term retention in the reticuloendothelial system. , …”

Section: Introductionmentioning

confidence: 99%

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Ultrasmall Antioxidant Cerium Oxide Nanoparticles for Regulation of Acute Inflammation

Kim

Hong

Mazaleuskaya

et al. 2021

ACS Appl. Mater. Interfaces

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Cerium oxide nanoparticles (CeONP), having potent antioxidant properties, are highly promising nanomaterials for treatment of diseases in which oxidative stress from excessive reactive oxygen species (ROS) plays a critical role in the pathogenesis and progression. However, most previously reported CeONP formulations were not efficiently cleared from the body, precluding their clinical translation. Herein, we report ultrasmall CeONP that can mitigate activation of macrophages and subsequent acute inflammation. It is found that these CeONP can effectively scavenge reactive species, inhibit macrophage activation, and minimize their recruitment and infiltration to the inflammation site, which lead to alleviation of edema and pain hypersensitivity. Moreover, we demonstrate that CeONP can be effectively excreted from the body within 24 h of systemic administration, minimizing long-term toxicity concerns. Altogether, our findings suggest that CeONP may be explored as both antioxidant and anti-inflammatory agents that can reduce acute inflammation with a better safety profile than existing nanoparticles.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ultrasmall Antioxidant Cerium Oxide Nanoparticles for Regulation of Acute Inflammation

Kim

Hong

Mazaleuskaya

et al. 2021

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

show abstract

“…Compared with small molecular drugs, these ultrasmall nanozymes with reasonable sizes can remain in the kidneys for a longer period and have better renal specificity. In previous reports, we demonstrated that ultrasmall nanomaterials with hydrodynamic diameter less than kidney threshold can effectively enrich in the kidneys, and can alleviate cisplatin as well as rhabdomyolysis-induced AKI owing to their multienzyme mimetic activity 43 - 46 .…”

Section: Introductionmentioning

confidence: 96%

Clinically translatable gold nanozymes with broad spectrum antioxidant and anti-inflammatory activity for alleviating acute kidney injury

Zhang

Younis

et al. 2021

Theranostics

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Rationale: Acute kidney injury (AKI) is associated with aberrant generation of oxidative species and inflammation, leading to high mortality of in-hospitalized patients. Although N -acetylcysteine (NAC) showed positive effects in alleviating contrast-induced AKI, the clinical applications are strongly restrained due to the low bioavailability, low renal accumulation, short renal retention time, and high dosage-induced toxicity. Methods: We addressed the clinical dilemma of NAC by developing ultrasmall gold nanoclusters (1-2 nm) capped with NAC (denoted as Au NCs-NAC) as a nanozyme-based antioxidant defense system for AKI alleviation. Rhabdomyolysis-induced AKI mice model was developed, and the same dose of free NAC (as a control) and NAC onto Au NCs (Au NCs-NAC) was used for in vivo investigation of AKI restoration. Results: The as-developed gold nanozyme exhibited high bioavailability and good physicochemical stability as compared to NAC. Meanwhile, Au NCs-NAC showed broad-spectrum antioxidant activity of Au NCs-NAC, offering in vitro renoprotective effects, as well as macrophages by relieving inflammation under hydrogen peroxide or lipopolysaccharide stimulation. Notably, owing to the smaller size than kidney threshold (5.5 nm), Au NCs-NAC displayed preferential renal enrichment (< 2 h) and longer retention (> 24 h) in AKI mice as revealed by fluorescence imaging, thereby largely enhancing the restoration of renal function in AKI mice than free NAC by protecting the kidneys from oxidative injury and inflammation without systemic toxicity, as demonstrated by tissues staining, inflammatory cytokines and biomarkers detection, and mice survival rate. Conclusion: Owing to the synergistic anti-inflammatory/antioxidative effects, and enhanced bioavailability and renal accumulation/retention, Au NCs-NAC displayed far superior therapeutic performance than NAC alone. This work will facilitate the development of high-performance antioxidative nanoplatforms, as well as overcome the clinical limitations of small molecular drugs for AKI treatment and other inflammatory diseases.

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“…Among these nanozymes, several nanomaterials have displayed promising effect on the elimination of reactive oxygen species (ROS), which could be employed as biomimetic antioxidants to regulate ROS homeostasis 31 , 33 – 36 . In particular, platinum nanoparticles (Pt NPs) as the substitute of natural enzymes for the treatment of oxidative stress-related diseases have gained growing interest, owing to their cytocompatibility and enzyme-like catalytic ability 37 – 39 . Pt NPs display the catalase (CAT)-like properties that decompose hydrogen peroxide (H 2 O 2 ) into H 2 O and oxygen (O 2 ).…”

Section: Introductionmentioning

confidence: 99%

Protective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia-reperfusion injury

Shi

et al. 2022

Nat Commun

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Therapeutic interventions of hepatic ischemia-reperfusion injury to attenuate liver dysfunction or multiple organ failure following liver surgery and transplantation remain limited. Here we present an innovative strategy by integrating a platinum nanoantioxidant and inducible nitric oxide synthase into the zeolitic imidazolate framework-8 based hybrid nanoreactor for effective prevention of ischemia-reperfusion injury. We show that platinum nanoantioxidant can scavenge excessive reactive oxygen species at the injury site and meanwhile generate oxygen for subsequent synthesis of nitric oxide under the catalysis of nitric oxide synthase. We find that such cascade reaction successfully achieves dual protection for the liver through reactive oxygen species clearance and nitric oxide regulation, enabling reduction of oxidative stress, inhibition of macrophage activation and neutrophil recruitment, and ensuring suppression of proinflammatory cytokines. The current work establishes a proof of concept of multifunctional nanotherapeutics against ischemia-reperfusion injury, which may provide a promising intervention solution in clinical use.

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Ultrasmall platinum nanozymes as broad-spectrum antioxidants for theranostic application in acute kidney injury

Cited by 44 publications

References 39 publications

Ultrasmall Antioxidant Cerium Oxide Nanoparticles for Regulation of Acute Inflammation

Ultrasmall Antioxidant Cerium Oxide Nanoparticles for Regulation of Acute Inflammation

Clinically translatable gold nanozymes with broad spectrum antioxidant and anti-inflammatory activity for alleviating acute kidney injury

Protective effect of platinum nano-antioxidant and nitric oxide against hepatic ischemia-reperfusion injury

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