Modulating Macrophage Polarization for Severe Acute Pancreatitis Therapy via Cisplatin-like Prussian Blue Nanozymes.

IF 13.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Theranostics Pub Date : 2025-08-11 eCollection Date: 2025-01-01 DOI:10.7150/thno.113523
Ling Wu, Rui Cai, Yuhang Li, Shuqi Liao, Yinghui Song, Yufeng Li, Jishan Li, Donghong Yu, Zhong Cao, Sulai Liu
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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.

通过顺铂样普鲁士蓝纳米酶调节巨噬细胞极化治疗重症急性胰腺炎。
原理:开发具有高生物安全性和抗炎特性的活性氧(ROS)抗氧化剂用于巨噬细胞调节在严重急性胰腺炎(SAP)治疗中仍然具有挑战性。在这里,我们设计了一种顺铂样六氰高铁钙普鲁士蓝纳米酶(Cri-Pt-CaFePB),它作为ROS清除剂调节巨噬细胞极化。方法:采用分步冻融法制备Cri-Pt-CaFePB,通过透射电镜和动态光散射对其结构和长期稳定性进行表征。随后,我们通过体外实验研究了Cri-Pt-CaFePB的细胞毒性和保护作用。采用荧光成像和ICP-MS监测其在体内的生物分布和药代动力学。利用生化试剂盒、免疫荧光、苏木精-伊红染色、western blot等方法明确Cri-Pt-CaFePB对SAP小鼠的体内治疗作用。结果:Pt(VI)前体与超微CaFePB纳米微球(~5 nm)共价配位,转化为Pt(II)类顺铂纳米酶抗氧化剂,在细胞和分子水平上表现出优异的ROS清除和抗炎作用,体外和体内均无毒性。密度泛函数理论模拟揭示了具有高过氧化物酶活性的Cri-Pt-CaFePB在抗炎症治疗中的关键作用。值得注意的是,经静脉给药后,Cri-Pt-CaFePB可通过下调CD86蛋白(M1标记物)表达和激活Arg-1蛋白(M2标记物),有效逆转SAP中的炎症损伤,抑制促炎细胞因子的表达,从而保护胰腺免受氧化应激损伤,诱导M1 - M2巨噬细胞再极化。结论:本研究强调了Cri-Pt-CaFePB纳米酶作为ROS清除剂调节巨噬细胞向M2表型极化的可行性,为纳米药物治疗提供了一种新的有效策略。
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来源期刊
Theranostics
Theranostics MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
25.40
自引率
1.60%
发文量
433
审稿时长
1 months
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.
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