{"title":"Modulating Macrophage Polarization for Severe Acute Pancreatitis Therapy via Cisplatin-like Prussian Blue Nanozymes.","authors":"Ling Wu, Rui Cai, Yuhang Li, Shuqi Liao, Yinghui Song, Yufeng Li, Jishan Li, Donghong Yu, Zhong Cao, Sulai Liu","doi":"10.7150/thno.113523","DOIUrl":null,"url":null,"abstract":"<p><p><b>Rationale:</b> Development of reactive oxygen species (ROS) antioxidants with high biosafety and anti-inflammatory properties for macrophage regulation in severe acute pancreatitis (SAP) therapy remains challenging. Here, we engineered a cisplatin-like calcium hexacyanoferrate Prussian blue nanozyme (Cri-Pt-CaFe<sub>PB</sub>) that functioned as a ROS scavenger to modulate macrophage polarization. <b>Methods:</b> The Cri-Pt-CaFe<sub>PB</sub> was prepared using a stepwise freeze-thaw method, and its structure and long-term stability were characterized by transmission electron microscope and dynamic light scatting. Subsequently, <i>in vitro</i> experiments were conducted to investigate the cytotoxicity and protective effects of Cri-Pt-CaFe<sub>PB</sub>. Fluorescence imaging and ICP-MS were applied to monitor its biodistribution and pharmacokinetics <i>in vivo</i>. Moreover, the biochemical kits, immunofluorescence, hematoxylin-eosin staining, and western blot were utilized to clarify <i>in vivo</i> therapeutic effect of Cri-Pt-CaFe<sub>PB</sub> in SAP mice. <b>Results:</b> Pt(VI) precursor was covalently coordinated with ultramicro CaFe<sub>PB</sub> nanospheres (~5 nm) and then converted into Pt(II) cisplatin-like nanozyme-based antioxidants, exhibiting exceptional ROS scavenging and anti-inflammatory effects at cellular and molecular levels with no toxicity <i>in vitro</i> or <i>in vivo</i>. Density functional theory simulation reveals the key role of Cri-Pt-CaFe<sub>PB</sub> with high peroxidase activity to the anti-inflammation treatment. Remarkably, the Cri-Pt-CaFe<sub>PB</sub> can protect the pancreas from oxidative stress damage and induce M1 to M2 macrophages repolarization after intravenous administration by downregulating CD86 protein expression (an M1 marker) and activating Arg-1 protein (an M2 marker), effectively reversing inflammatory damage in SAP and inhibiting the expression of proinflammatory cytokines. <b>Conclusions:</b> This study highlights the feasibility of Cri-Pt-CaFe<sub>PB</sub> nanozymes as ROS scavengers to regulate macrophage polarization towards M2 phenotype, which offers a novel effective nanomedicine strategy.</p>","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":"15 17","pages":"8916-8934"},"PeriodicalIF":13.3000,"publicationDate":"2025-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12439267/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Theranostics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/thno.113523","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0
Abstract
Rationale: Development of reactive oxygen species (ROS) antioxidants with high biosafety and anti-inflammatory properties for macrophage regulation in severe acute pancreatitis (SAP) therapy remains challenging. Here, we engineered a cisplatin-like calcium hexacyanoferrate Prussian blue nanozyme (Cri-Pt-CaFePB) that functioned as a ROS scavenger to modulate macrophage polarization. Methods: The Cri-Pt-CaFePB was prepared using a stepwise freeze-thaw method, and its structure and long-term stability were characterized by transmission electron microscope and dynamic light scatting. Subsequently, in vitro experiments were conducted to investigate the cytotoxicity and protective effects of Cri-Pt-CaFePB. Fluorescence imaging and ICP-MS were applied to monitor its biodistribution and pharmacokinetics in vivo. Moreover, the biochemical kits, immunofluorescence, hematoxylin-eosin staining, and western blot were utilized to clarify in vivo therapeutic effect of Cri-Pt-CaFePB in SAP mice. Results: Pt(VI) precursor was covalently coordinated with ultramicro CaFePB nanospheres (~5 nm) and then converted into Pt(II) cisplatin-like nanozyme-based antioxidants, exhibiting exceptional ROS scavenging and anti-inflammatory effects at cellular and molecular levels with no toxicity in vitro or in vivo. Density functional theory simulation reveals the key role of Cri-Pt-CaFePB with high peroxidase activity to the anti-inflammation treatment. Remarkably, the Cri-Pt-CaFePB can protect the pancreas from oxidative stress damage and induce M1 to M2 macrophages repolarization after intravenous administration by downregulating CD86 protein expression (an M1 marker) and activating Arg-1 protein (an M2 marker), effectively reversing inflammatory damage in SAP and inhibiting the expression of proinflammatory cytokines. Conclusions: This study highlights the feasibility of Cri-Pt-CaFePB nanozymes as ROS scavengers to regulate macrophage polarization towards M2 phenotype, which offers a novel effective nanomedicine strategy.
期刊介绍:
Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.