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ID 116134
著者
Hirata, Yuma Tokushima University
Tashima, Riho Tokushima University
Mitsuhashi, Naoto ProteNova
Yoneda, Shintaro Tokushima University
福田, 達也 Tokushima University|Wakayama Medical University KAKEN研究者をさがす
Majima, Eiji ProteNova
キーワード
Antibody-modified liposomes
modified protein A
active targeting
資料タイプ
学術雑誌論文
抄録
Modification with antibodies is a useful strategy for the delivery of nanoparticles to target cells. However, the complexity of the required chemical modifications makes them time-consuming and low efficiency, and the orientation of the antibody is challenging to control. To develop a simple, fast, effective, and orientation-controllable technology, we employed staphylococcal protein A, which can bind to the Fc region of antibodies, as a tool for conjugating antibodies to nanoparticles. Specifically, we modified the C-domain dimer of protein A to contain a lysine cluster to create a molecule, DPACK, that would electrostatically bind to anionic liposomes. Using this protein, antibody-modified liposomes can be prepared in 35 minutes with two steps: (1) interaction of DPACK with liposomes and (2) interaction of an antibody with DPACK-modified liposomes. Binding efficiencies of DPACK with liposomes and IgG with DPACK-modified liposomes were 75% and 72-84%, respectively. Uptake of liposomes modified with anti-epidermal growth factor receptor (EGFR) antibodies via DPACK by EGFR-expressing cancer cells was significantly higher than that of unmodified liposomes, and the liposomes accumulated in tumors and colocalized with EGFR. This simple, fast, effective and orientation-controllable technology for preparing antibody-modified liposomes will be useful for active targeting drug delivery.
掲載誌名
International Journal of Pharmaceutics
ISSN
03785173
cat書誌ID
AA00680771
AA11530828
出版者
Elsevier
607
開始ページ
120966
発行日
2021-08-02
権利情報
© 2021. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
著者版
部局
薬学系