サトウ　アツシ   佐藤　淳    所属   応用生物学部 応用生物学科    職種   教授
言語種別	英語
発行・発表の年月	2023/12
形態種別	学術論文
査読	査読あり
標題	Enhanced intracellular uptake of an albumin fusion protein in cancer cells by its forced cell surface recruitment
執筆形態	共著
掲載誌名	European Journal of Pharmaceutical Sciences
掲載区分	国外
出版社・発行元	Elsevier B.V.
担当区分	責任著者
著者・共著者	Daisuke Kurimoto, Atsushi Sato
概要	Albumin fusion or conjugation is a well-established technique for tumor delivery and is mainly mediated by albumin-induced caveolae-dependent endocytosis. We report that caveolae-dependent endocytic signaling activated by human serum albumin (HSA) is not sufficiently strong to induce cellular uptake, mainly due to its electrostatic repulsion from the negatively charged cell surface sulfated glycosaminoglycans (GAGs), and fusion of the cell-surface-retained protein with HSA is an effective strategy to activate the HSA-induced endocytic signal, thereby improving its intracellular uptake. In this study, human lactoferrin (hLF), a protein that accumulates on the cell surface along with GAGs, was selected for delivery into human lung adenocarcinoma PC-14 cells. When added exogenously, hLF-fused HSA (hLF-HSA) was successfully endocytosed, whereas the simultaneous addition of HSA and hLF did not result in endocytosis, indicating less efficient activation of endocytic signaling by HSA alone and the importance of its fusion. Importantly, the treatment of cells with chlorate, a known inhibitor of GAG sulfation, dramatically suppressed the endocytosis of hLF-HSA owing to the loss of the hLF-GAG interaction. Therefore, the cell-surface localization of HSA imposed by fusion with the cell-surface-retained protein enhances its binding to the relevant receptor, which improves intracellular delivery as an albumin-fusion platform.
外部リンクURL	https://www.sciencedirect.com/science/article/pii/S092809872300221X?via%3Dihub