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ID 117236
Author
Khatun, Anowara Tokushima University
Hasan, Mahadi Tokushima University|Tokyo Biochemical Research Foundation|Kanazawa University
El-Emam, Mahran Mohamed Abd Tokushima University|Zagazig University
Fukuta, Tatsuya Tokushima University|Wakayama Medical University KAKEN Search Researchers
Mimura, Miyuki Tokushima University
Tashima, Riho Tokushima University
Yoneda, Shintaro Tokushima University
Yoshimi, Shintaro Tokushima University
Keywords
weak electric current
enhanced permeability and retention effect
nanoparticle
anticancer therapy
Content Type
Journal Article
Description
Delivery of medicines using nanoparticles via the enhanced permeability and retention (EPR) effect is a common strategy for anticancer chemotherapy. However, the extensive heterogeneity of tumors affects the applicability of the EPR effect, which needs to overcome for effective anticancer therapy. Previously, we succeeded in the noninvasive transdermal delivery of nanoparticles by weak electric current (WEC) and confirmed that WEC regulates the intercellular junctions in the skin by activating cell signaling pathways (J. Biol. Chem., 289, 2014, Hama et al.). In this study, we applied WEC to tumors and investigated the EPR effect with polyethylene glycol (PEG)-modified doxorubicin (DOX) encapsulated nanoparticles (DOX-NP) administered via intravenous injection into melanoma-bearing mice. The application of WEC resulted in a 2.3-fold higher intratumor accumulation of nanoparticles. WEC decreased the amount of connexin 43 in tumors while increasing its phosphorylation; therefore, the enhancing of intratumor delivery of DOX-NP is likely due to the opening of gap junctions. Furthermore, WEC combined with DOX-NP induced a significant suppression of tumor growth, which was stronger than with DOX-NP alone. In addition, WEC alone showed tumor growth inhibition, although it was not significant compared with non-treated group. These results are the first to demonstrate that effective anticancer therapy by combination of nanoparticles encapsulating chemotherapeutic agents and WEC.
Journal Title
Biological and Pharmaceutical Bulletin
ISSN
13475215
NCID
AA11696048
Publisher
The Pharmaceutical Society of Japan
Volume
45
Issue
2
Start Page
194
End Page
199
Published Date
2022-02-01
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Pharmaceutical Sciences