肝脏疾病和癌症的发病和进展已被证明受到过度活跃的巨噬细胞和成纤维细胞的影响。因此，开发抑制这些细胞活化的方法已成为当务之急。在这项研究之前，已经创建了一种针对肝巨噬细胞（库普弗细胞）或成纤维细胞中表达的甘露糖受体的甘露糖化白蛋白（Man-HSA）。在此，我们报告基于 Man-HSA 的医学治疗的进展。为了针对库普弗细胞产生的活性氧或炎症，我们通过在Man-HSA中引入硫醇基团，开发了一种纳米抗氧化剂，即多硫醇化(SH)-Man-HSA，或一种纳米抗炎药物，即，Man-HSA-IFNα2b，通过融合Man-HSA和IFNα2b。 SH-Man-HSA 或 Man-HSA-IFNα2b 分别减轻库普弗细胞源性氧化应激或炎症，从而抑制肝损伤并全面提高急性和慢性肝损伤小鼠的存活率。肿瘤相关巨噬细胞（TAM）和癌症相关成纤维细胞（CAF）都存在于难治性癌症的基质中，也表达甘露糖受体。因此，合成了单聚乙二醇修饰的Man-HSA（monoPEG-Man-HSA）作为靶向TAM/CAF的新型药物递送载体。 monoPEG-Man-HSA 与紫杉醇的复合物通过减少 TAM/CAF 的数量和基质面积来抑制肿瘤生长。在本研究中，我们重点关注巨噬细胞和成纤维细胞中表达的甘露糖受体，并开发了针对这些细胞的药物递送载体。考虑到HSA优异的载药能力和高生物相容性，预计这项研究将为创新药物疗法铺平道路，以治疗未满足的医疗需求，即难治性肝病和癌症。

The onset and progression of liver diseases and cancer have shown to be affected by over-active macrophages and fibroblasts. Therefore, developing methods to suppress the activation of these cells has become an urgent task. Prior to this study, a mannosylated-albumin (Man-HSA) that targets mannose receptors expressed in hepatic macrophages (Kupffer cells) or fibroblasts was created. Here, we report on the development of medical treatments based on Man-HSA. To target the reactive oxygen species or inflammation derived from Kupffer cells, we developed a nano-antioxidant, i.e., polythiolated (SH)-Man-HSA, by introducing thiol groups into Man-HSA, or a nano-anti-inflammatory drug, i.e., Man-HSA-IFNα2b, by fusing Man-HSA and IFNα2b. SH-Man-HSA or Man-HSA-IFNα2b attenuated Kupffer cell-derived oxidative stress or inflammation, respectively, resulting in the suppression of liver damage and overall improvement of the survival rate in mice with acute and chronic liver injuries. Tumor-associated macrophages (TAM) and cancer-associated fibroblasts (CAF), both of which are present in the stroma of intractable cancers, also express mannose receptors. Thus, mono-polyethylene glycol modified Man-HSA (monoPEG-Man-HSA) was synthesized as a novel drug delivery carrier targeting TAM/CAF. A complex of monoPEG-Man-HSA with paclitaxel suppressed tumor growth by decreasing the number of TAM/CAF and the stroma area. For the present study, we focused on the mannose receptors expressed in macrophages and fibroblasts, and developed drug delivery carriers that target these cells. Considering the excellent drug-carrying capacity and high biocompatibility of HSA, it is expected that this research will pave the way for innovative pharmacotherapy to treat unmet medical needs, i.e., intractable liver diseases and cancer.