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ID 116134
Author
Hirata, Yuma Tokushima University
Tashima, Riho Tokushima University
Mitsuhashi, Naoto ProteNova
Yoneda, Shintaro Tokushima University
Fukuta, Tatsuya Tokushima University|Wakayama Medical University KAKEN Search Researchers
Majima, Eiji ProteNova
Keywords
Antibody-modified liposomes
modified protein A
active targeting
Content Type
Journal Article
Description
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.
Journal Title
International Journal of Pharmaceutics
ISSN
03785173
NCID
AA00680771
AA11530828
Publisher
Elsevier
Volume
607
Start Page
120966
Published Date
2021-08-02
Rights
© 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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Author
departments
Pharmaceutical Sciences