Show simple item record

dc.contributor.authorKinoshita, R.
dc.contributor.authorIshima, Y.
dc.contributor.authorIkeda, M.
dc.contributor.authorKragh-Hansen, U.
dc.contributor.authorFang, J.
dc.contributor.authorNakamura, H.
dc.contributor.authorChuang, Victor
dc.contributor.authorTanaka, R.
dc.contributor.authorMaeda, H.
dc.contributor.authorKodama, A.
dc.contributor.authorWatanabe, H.
dc.contributor.authorMaeda, H.
dc.contributor.authorOtagiri, M.
dc.contributor.authorMaruyama, T.
dc.date.accessioned2017-01-30T11:43:11Z
dc.date.available2017-01-30T11:43:11Z
dc.date.created2015-12-10T04:25:56Z
dc.date.issued2015
dc.identifier.citationKinoshita, R. and Ishima, Y. and Ikeda, M. and Kragh-Hansen, U. and Fang, J. and Nakamura, H. and Chuang, V. et al. 2015. S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes. Journal of Controlled Release. 217: pp. 1-9.
dc.identifier.urihttp://hdl.handle.net/20.500.11937/14345
dc.identifier.doi10.1016/j.jconrel.2015.08.036
dc.description.abstract

© 2015 Elsevier B.V. All rights reserved. The enhanced permeability and retention (EPR) effect is a unique phenomenon of solid tumors, and it can serve as a basis for the development of macromolecular anticancer therapy. We have previously found that recombinant human serum albumin dimer, and especially its S-nitrosated form (SNO-HSA-Dimer), is an enhancer of the EPR effect. In this study, we investigated the influence of SNO-HSA-Dimer on the anti-tumor effect of two types of macromolecular anti-tumor drugs, namely N-(2-hydroxypropyl)methacrylamide polymer conjugated with zinc protoporphyrin, which forms micelles and can be used for fluorescence studies. The other was PEGylated liposomal doxorubicin (Doxil), a typical example of a stealth liposome approved for medical usage. In mice having C26 tumors with highly permeable vasculature, SNO-HSA-Dimer increases tumor accumulation of the drugs by a factor 3-4 and thereby their anti-tumor effects. Experiments with Evans blue revealed increased EPR effect in all parts of the tumor. Furthermore, SNO-HSA-Dimer improves the anti-metastatic effects of Doxil and reduces its minor uptake in non-tumorous organs such as liver and kidney. Tumor accumulation of Doxil in B16 tumors, which are characterized by a low permeable vasculature, increased even more (6-fold) in the presence of SNO-HSA-Dimer, and the improved accumulation lead to decreased tumor volume and increased survival of the animals. The administration of SNO-HSA-Dimer itself is safe, because it has no effect on blood pressure, heart rate or on several biochemical parameters. The present findings indicate that SNO-HSA-Dimer is promising for enhancing the EPR effect and consequently the specific, therapeutic effects of macromolecular anticancer drugs.

dc.publisherElsevier
dc.titleS-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes
dc.typeJournal Article
dcterms.source.volume217
dcterms.source.startPage1
dcterms.source.endPage9
dcterms.source.issn0168-3659
dcterms.source.titleJournal of Controlled Release
curtin.departmentSchool of Pharmacy
curtin.accessStatusFulltext not available


Files in this item

FilesSizeFormatView

There are no files associated with this item.

This item appears in the following Collection(s)

Show simple item record