S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes
© 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 especi...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal Article |
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Elsevier
2015
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| Online Access: | http://hdl.handle.net/20.500.11937/14345 |
| _version_ | 1848748598376792064 |
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| author | Kinoshita, R. Ishima, Y. Ikeda, M. Kragh-Hansen, U. Fang, J. Nakamura, H. Chuang, Victor Tanaka, R. Maeda, H. Kodama, A. Watanabe, H. Maeda, H. Otagiri, M. Maruyama, T. |
| author_facet | Kinoshita, R. Ishima, Y. Ikeda, M. Kragh-Hansen, U. Fang, J. Nakamura, H. Chuang, Victor Tanaka, R. Maeda, H. Kodama, A. Watanabe, H. Maeda, H. Otagiri, M. Maruyama, T. |
| author_sort | Kinoshita, R. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 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. |
| first_indexed | 2025-11-14T07:07:35Z |
| format | Journal Article |
| id | curtin-20.500.11937-14345 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T07:07:35Z |
| publishDate | 2015 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-143452017-09-13T14:06:28Z S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes Kinoshita, R. Ishima, Y. Ikeda, M. Kragh-Hansen, U. Fang, J. Nakamura, H. Chuang, Victor Tanaka, R. Maeda, H. Kodama, A. Watanabe, H. Maeda, H. Otagiri, M. Maruyama, T. © 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. 2015 Journal Article http://hdl.handle.net/20.500.11937/14345 10.1016/j.jconrel.2015.08.036 Elsevier restricted |
| spellingShingle | Kinoshita, R. Ishima, Y. Ikeda, M. Kragh-Hansen, U. Fang, J. Nakamura, H. Chuang, Victor Tanaka, R. Maeda, H. Kodama, A. Watanabe, H. Maeda, H. Otagiri, M. Maruyama, T. S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes |
| title | S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes |
| title_full | S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes |
| title_fullStr | S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes |
| title_full_unstemmed | S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes |
| title_short | S-Nitrosated human serum albumin dimer as novel nano-EPR enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes |
| title_sort | s-nitrosated human serum albumin dimer as novel nano-epr enhancer applied to macromolecular anti-tumor drugs such as micelles and liposomes |
| url | http://hdl.handle.net/20.500.11937/14345 |