Ca/Fe-Based Nanozymes Relieve Severe Acute Pancreatitis by Ferroptosis Regulation and Reactive Oxygen Species Scavenging

Li, Yuhang; Cai, Rui; Chen, Kang; Zhang, Yujing; Xu, Chi; Sun, Boxing; Jiang, Yu; Tan, Chongqing; Peng, Chuang; Song, Yinghui; Wu, Lei; Liu, Sulai

doi:10.1021/acsanm.3c01697

Cited by 3 publications

References 39 publications

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Safety Landscape of Therapeutic Nanozymes and Future Research Directions

Tagaras,

Song,

Sahar

et al. 2024

Advanced Science

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Oxidative stress and inflammation are at the root of a multitude of diseases. Treatment of these conditions is often necessary but current standard therapies to fight excessive reactive oxygen species (ROS) and inflammation are often ineffective or complicated by substantial safety concerns. Nanozymes are emerging nanomaterials with intrinsic enzyme‐like properties that hold great promise for effective cancer treatment, bacterial elimination, and anti‐inflammatory/anti‐oxidant therapy. While there is rapid progress in tailoring their catalytic activities as evidenced by the recent integration of single‐atom catalysts (SACs) to create next‐generation nanozymes with superior activity, selectivity, and stability, a better understanding and tuning of their safety profile is imperative for successful clinical translation. This review outlines the current applied safety assessment approaches and provides a comprehensive summary of the safety knowledge of therapeutic nanozymes. Overall, nanozymes so far show good in vitro and in vivo biocompatibility despite considerable differences in their composition and enzymatic activities. However, current safety investigations mostly cover a limited set of basic toxicological endpoints, which do not allow for a thorough and deep assessment. Ultimately, remaining research gaps that should be carefully addressed in future studies are highlighted, to optimize the safety profile of therapeutic nanozymes early in their pre‐clinical development.

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Safety Landscape of Therapeutic Nanozymes and Future Research Directions

Tagaras,

Song,

Sahar

et al. 2024

Advanced Science

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Iron–Calcium-Codoped Mesoporous Antimicrobial Nanoagents for Healing of Wounds Infected by Bacteria

Bu,

Hu,

Zheng

et al. 2024

ACS Appl. Nano Mater.

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Chronic wounds with multidrug-resistant bacterial infections substantially delay the healing procedure and correlate with clinical implications, including pain increase and quality of life reduction. Therapeutic approaches that could kill bacteria and promote wound healing are highly desired for the treatment of chronic nonhealing wounds. Metal oxide-based nanoagents show increasing potential as a burgeoning type of antibiotic for multidrug-resistant bacterial infections. In this study, we developed two kinds of Fe-and Ca-incorporating mesoporous silica nanoparticles (FeCaSi) via a simple and practicable strategy. They can be applied for the administration of bacterial infection and wound healing. The antibacterial properties of FeCaSi nanoagents include bacterial cell wall capturing and subsequent reactive oxygen species (ROS)-producing activity; besides, the killing capacity can be tailored by adjusting the ratio between Fe and Ca to be 4:3 (FeCaSi4:3), which is optimal for the eradication of drug-resistant Escherichia coli and Staphylococcus aureus infection. Furthermore, treatment with FeCaSi4:3 could reduce the bacteria in the skin, promote collagen deposition, and accelerate the healing of bacterial-infected wounds in mice. Our study provided a simple but powerful way to engineer metal oxide mesoporous nanoparticles for antibacterial therapy.

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A Dual-Targeted Nanocapsule Inhibitor Alleviates Severe Acute Pancreatitis via Cytokine and NLRP3 Inflammasome Regulation

Wu,

Liao,

et al. 2024

Preprint

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Severe acute pancreatitis (SAP), a special type of acute abdomen, lacks effective treatment methods for clinical diagnosis because of its complex etiology and unclear pathogenesis. Herein, we engineered a structurally controllable gold-doped Prussian blue analogues-based nanozyme by optimizing the preparation procedure as a dual-targeted inhibitor of the NLRP3 inflammasome and inflammatory cytokine pathways for treating SAP. The as-synthesized nanomaterials with different structures, including nanocapsular (CaAuHCF), ultramicro nanocube (CAHCF-Au), and nanocube (CaHCF) structures, exhibit multienzyme-like activities, such as peroxidase (POD), glutathione peroxidase (GPx), and superoxide dismutase (SOD), which are dependent on their structure. Density functional theory (DFT) simulations revealed the underlying mechanisms of differences in reactivity among nanomaterials with different compositions and structures, indicating that the POD catalytic activity of CaAuHCF nanocapsules plays a leading role under physiological conditions. In vitro or vivo experiments confirmed that CaAuHCF nanocapsules can efficiently remove exogenous and endogenous reactive oxygen species (ROS) at the cellular level and are nontoxic. Importantly, the CaAuHCF nanozyme not only is a cytokine regulator that can mediate the level of cytokine factors related to proinflammatory cell pathways (IL-6, TNF-α, and IL-1β) but also acts as an inhibitor of NLRP3 activation to effectively relieve the inflammatory symptoms of SAP through preventing the cleavage of Gasdermin-D into Gasdermin-N via targeted inhibition of cleaved Caspase-1 activation, thus suppressing the pyroptosis of pancreatic and immune cells. Overall, our data highlight the feasibility of CaAuHCF nanocapsules as dual-targeted inhibitors of cytokines and the NLRP3 inflammasome and provide potential nanozyme-based antioxidants for SAP treatment.

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Ca/Fe-Based Nanozymes Relieve Severe Acute Pancreatitis by Ferroptosis Regulation and Reactive Oxygen Species Scavenging

Cited by 3 publications

References 39 publications

Safety Landscape of Therapeutic Nanozymes and Future Research Directions

Safety Landscape of Therapeutic Nanozymes and Future Research Directions

Iron–Calcium-Codoped Mesoporous Antimicrobial Nanoagents for Healing of Wounds Infected by Bacteria

A Dual-Targeted Nanocapsule Inhibitor Alleviates Severe Acute Pancreatitis via Cytokine and NLRP3 Inflammasome Regulation

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