Clinical Applications of Cell-Specific Carriers Based on Glycosylated Albumin

Abstract

Over-activated macrophages and/or fibroblasts have shown involvement in the onset and progression of various diseases, including hepatitis and cancer. Therefore, the development of techniques to inhibit the activation of these cells has become an urgent challenge. Prior to this study, a mannosylated-human serum albumin (Man-HSA) was created to target mannose receptors expressed on Kupffer cells. Here, applications of Man-HSA for medical treatments are reported. To target the reactive oxygen species or inflammation derived from Kupffer cells, a nano-antioxidant, i.e., SH-Man-HSA, produced by introducing thiol groups into Man-HSA, or a nano-anti-inflammatory drug, i.e., Man-HSA-interferonα2b (IFNα2b), produced by fusing Man-HSA and IFNα2b was developed. SH-Man-HSA or Man-HSA-IFNα2b mitigated oxidative stress or inflammation derived from Kupffer cells, resulting in the suppression of liver damage and an overall improvement in the survival rate of mice model for acute and chronic hepatitis. Tumor-associated macrophages (TAM) and cancer-associated fibroblasts (CAF), both of which are present in the stroma of intractable cancers, also express mannose receptors. Therefore, mono-polyethylene glycol modified Man-HSA (monoPEG-Man-HSA) was fabricated as a novel drug delivery carrier targeting cancer stromal cells, i.e., TAM-CAF. monoPEG-Man-HSA-paclitaxel complex inhibited tumor growth by decreasing the number of TAM-CAF and the stroma area. In this way, our study focused on the mannose receptors expressed on macrophages and fibroblasts, and applied Man-HSA for medical treatments. Given that the excellent drug-carrying capacity and high biocompatibility of HSA itself, this research also paves the way for innovative pharmacotherapy to treat macrophage- and fibroblast-associated diseases outside of hepatitis and cancer.