Early detection and timely intervention are essential to prevent liver fibrosis from progressing to cirrhosis or hepatocellular carcinoma. Herein, utilizing the enhanced ferritin‐manganese interaction by nanoplatinum growth, a novel ferritin‐platinum‐manganese magnetic resonance nanoplatform with RGD grafting and metformin loading (FNMMR) is developed. RGD can enhance the targeting ability of the nanoplatform toward integrin αVβ3 on activated hepatic stellate cells (aHSCs) in liver fibrosis. Systemic delivery of FNMMR shows clear degree‐dependent magnetic resonance contrast enhancement in liver fibrosis. 3D reconstruction techniques and histogram‐based features are achieved to qualitatively and quantitatively analyze the inhomogeneous liver fibrosis areas. FNMMR with catalase‐like activity can catalyze the generation of O2 to alleviate the liver fibrosis hypoxia and inhibit the expression of HIF‐1α, blocking the TGF‐β1/Smad signaling pathway. In addition, metformin shows synergy with HIF‐1α reduction in blocking the TGF‐β1/Smad pathway, effectively inhibiting the activation of HSCs and reducing collagen formation. Furthermore, FNMMR can achieve real‐time anti‐fibrotic therapy monitoring by magnetic resonance imaging. Importantly, no obvious side effects can be observed in both histological and hematology examinations. Therefore, this work presents a novel nanoplatform for accurate liver fibrosis diagnosis and synergistic anti‐fibrotic therapy with real‐time monitoring.

中文翻译：

---

通过纳米铂生长增强铁蛋白-锰相互作用，实现肝纤维化 3D 磁共振可视化和实时监测协同疗法


早期发现和及时干预对于防止肝纤维化发展为肝硬化或肝细胞癌至关重要。在此，利用纳米铂生长增强的铁蛋白-锰相互作用，开发了一种具有 RGD 接枝和二甲双胍负载 （FNMMR） 的新型铁蛋白-铂-锰磁共振纳米平台。RGD 可以增强纳米平台对肝纤维化中活化的肝星状细胞 （aHSC） 上整合素 αVβ3 的靶向能力。FNMMR 的全身递送在肝纤维化中显示出明显的程度依赖性磁共振对比增强。实现 3D 重建技术和基于直方图的特征，以定性和定量分析不均匀的肝纤维化区域。具有过氧化氢酶样活性的 FNMMR 可催化 O2 的产生，以减轻肝纤维化缺氧并抑制 HIF-1α 的表达，阻断 TGF-β1/Smad 信号通路。此外，二甲双胍在阻断 TGF-β1/Smad 通路方面显示出与 HIF-1α 减少的协同作用，有效抑制 HSC 的激活并减少胶原蛋白的形成。此外，FNMMR 可以通过磁共振成像实现实时抗纤维化治疗监测。重要的是，在组织学和血液学检查中均未观察到明显的副作用。因此，这项工作提出了一种新的纳米平台，用于准确诊断肝纤维化和协同抗纤维化治疗，并进行实时监测。