Noninvasive and precise diagnosis of hepatic fibrosis is very important for the preventive therapeutic regimen of hepatic cirrhosis and cancer. In this study, we fabricated T₁ contrast Mn-porphyrin (MnTPPS₄)/retinoic acid-chitosan ionic-complex nanoparticles (MRC NPs). The functional properties of MRC NPs were evaluated via transmission electron microscopy (TEM) imaging, release study, cytotoxicity assay, hepatocyte-specific uptake assay, and magnetic resonance (MR) imaging study. TEM images confirmed the typical structure of an ionic-complex NPs with around 100–200 nm of diameter. MnTPPS₄ is released from MRC NPs for up to 24 hr in controlled pattern which implies that more reliable and convenient hepatic MR imaging is possible using of MRC NPs in clinical practice. Hepatocytes uptake assay proved retinoic acid-specific targeting of MRC NPs. The same results were observed in animal pharmacokinetic studies. In vitro MR phantom study, MRC NPs showed an increased T₁ relaxivity (r₁ = 6.772 mM⁻¹ s⁻¹) in comparison with 3.242 mM⁻¹ s⁻¹ of MnTPPS₄. The result was confirmed again in vivo MR imaging studies. Taken together, MRC NPs displayed a potential for noninvasive diagnostic T₁ MR imaging of hepatic fibrosis with improved target specificity and prolonged MR imaging time window.

中文翻译：

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维甲酸偶联壳聚糖/锰卟啉离子复合纳米粒子用于改善肝纤维化的 T1 对比 MR 成像

肝纤维化的无创、精准诊断对于肝硬化和肝癌的预防性治疗方案非常重要。在这项研究中，我们制造了 T ₁对比锰卟啉 (MnTPPS ₄ )/视黄酸-壳聚糖离子复合纳米粒子 (MRC NPs)。通过透射电子显微镜 (TEM) 成像、释放研究、细胞毒性测定、肝细胞特异性摄取测定和磁共振 (MR) 成像研究评估 MRC NPs 的功能特性。TEM 图像证实了直径约为 100-200 nm 的离子复合 NP 的典型结构。锰TPPS ₄以受控模式从 MRC NPs 释放长达 24 小时，这意味着在临床实践中使用 MRC NPs 可以进行更可靠和方便的肝脏 MR 成像。肝细胞摄取试验证明了 MRC NPs 的视黄酸特异性靶向。在动物药代动力学研究中观察到相同的结果。在体外 MR 体模研究中，与MnTPPS _{4的 3.242 mM} ^-1  s ^-1相比，MRC NPs 显示出增加的 T ₁弛豫率 ( r ₁  = 6.772 mM ^-1  s ^-1 ) 。该结果在体内 MR 成像研究中再次得到证实。总之，MRC NPs 显示出无创诊断 T _1的潜力肝纤维化的 MR 成像具有改进的靶特异性和延长的 MR 成像时间窗。