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The effect of liposomal size on the targeted delivery of doxorubicin to Integrin alpha v beta 3-expressing tumor endothelial cells

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Title: The effect of liposomal size on the targeted delivery of doxorubicin to Integrin alpha v beta 3-expressing tumor endothelial cells
Authors: Kibria, Golam Browse this author
Hatakeyama, Hiroto Browse this author →KAKEN DB
Ohga, Noritaka Browse this author
Hida, Kyoko Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Keywords: Size of liposomes
Ligand multivalency
Drug-resistant cancer
Tumor vasculature targeting
Anti-angiogenic effect
Issue Date: Jul-2013
Publisher: Elsevier
Journal Title: Biomaterials
Volume: 34
Issue: 22
Start Page: 5617
End Page: 5627
Publisher DOI: 10.1016/j.biomaterials.2013.03.094
PMID: 23623323
Abstract: Size of the liposomes (LPs) specially governs its biodistribution. In this study, LPs were developed with controlled sizes, where variation in LP size dictates the ligand receptor interaction, cellular internalization and its distribution within the tumor microenvironment. The therapeutic efficacies of doxorubicin (DOX)-loaded RGD modified small size (similar to 100 nm in diameter, dnm) and large size (similar to 300 dnm) PEGylated LPs (RGD-PEG-LPs) were compared to that of Doxil (a clinically used DOX-loaded PEG-LP, similar to 100 dnm) in DOX resistant OSRC-2 (Renal cell carcinoma, RCC) tumor xenografts. Doxil, which accumulated in tumor tissue via the enhanced permeability and retention (EPR) effect, failed to suppress tumor growth. Small size RGD-PEG-LP, that targets the tumor endothelial cells (TECs) and extravasates to tumor cells, failed to provide anti-tumor effect. Large size RGD-PEG-LP preferentially targets the TECs via minimization of the EPR effect, and significantly reduced the tumor growth, which was exerted through its strong anti-angiogenic activity on the tumor vasculature rather than having a direct effect on DOX resistant RCC. The prepared large size RGD-PEG-LP that targets the TECs via interacting with Integrin alpha v beta 3, is a potentially effective and alternate therapeutic strategy for the treatment of DOX resistant tumor cells by utilizing DOX, in cases where Doxil is ineffective. (C) 2013 Elsevier Ltd. All rights reserved.
Type: article (author version)
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 畠山 浩人

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