Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control
The current enhanced permeability and retention (EPR)-based approved nanomedicines have had little impact in terms of prolongation of overall survival in patients with cancer. For example, the two Phase III trials comparing Doxil®, the first nanomedicine approved by the US Food and Drug Administrati...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2015
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| Online Access: | https://hdl.handle.net/10356/107443 http://hdl.handle.net/10220/25625 |
| _version_ | 1826110383395438592 |
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| author | Shen, Yao An Shyu, Ing Luen Lu, Maggie He, Chun Lin Hsu, Yen Mei Liang, Hsiang Fa Liu, Chih Peng Liu, Ren Shyan Shen, Biing Jiun Wei, Yau Huei Chuang, Chi Mu |
| author2 | School of Humanities and Social Sciences |
| author_facet | School of Humanities and Social Sciences Shen, Yao An Shyu, Ing Luen Lu, Maggie He, Chun Lin Hsu, Yen Mei Liang, Hsiang Fa Liu, Chih Peng Liu, Ren Shyan Shen, Biing Jiun Wei, Yau Huei Chuang, Chi Mu |
| author_sort | Shen, Yao An |
| collection | NTU |
| description | The current enhanced permeability and retention (EPR)-based approved nanomedicines have had little impact in terms of prolongation of overall survival in patients with cancer. For example, the two Phase III trials comparing Doxil®, the first nanomedicine approved by the US Food and Drug Administration, with free doxorubicin did not find an actual translation of the EPR effect into a statistically significant increase in overall survival but did show less cardiotoxicity. In the current work, we used a two-factor factorial experimental design with intraperitoneal versus intravenous delivery and nanomedicine versus free drug as factors to test our hypothesis that regional (intraperitoneal) delivery of nanomedicine may better increase survival when compared with systemic delivery. In this study, we demonstrate that bypassing, rather than exploiting, the EPR effect via intraperitoneal delivery of nanomedicine harboring a sustained-release function demonstrates dual pharmacokinetic advantages, producing more efficient tumor control and suppressing the expression of stemness markers, epithelial-mesenchymal transition, angiogenesis signals, and multidrug resistance in the tumor microenvironment. Metastases to vital organs (eg, lung, liver, and lymphatic system) are also better controlled by intraperitoneal delivery of nanomedicine than by standard systemic delivery of the corresponding free drug. Moreover, the intraperitoneal delivery of nanomedicine has the potential to replace hyperthermic intraperitoneal chemotherapy because it shows equal efficacy and lower toxicity. In terms of efficacy, exploiting the EPR effect may not be the best approach for developing a nanomedicine. Because intraperitoneal chemotherapy is a type of regional chemotherapy, the pharmaceutical industry might consider the regional delivery of nanomedicine as a valid alternative pathway to develop their nanomedicine(s) with the goal of better tumor control in the future. |
| first_indexed | 2024-10-01T02:33:30Z |
| format | Journal Article |
| id | ntu-10356/107443 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:33:30Z |
| publishDate | 2015 |
| record_format | dspace |
| spelling | ntu-10356/1074432022-02-16T16:27:33Z Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control Shen, Yao An Shyu, Ing Luen Lu, Maggie He, Chun Lin Hsu, Yen Mei Liang, Hsiang Fa Liu, Chih Peng Liu, Ren Shyan Shen, Biing Jiun Wei, Yau Huei Chuang, Chi Mu School of Humanities and Social Sciences DRNTU::Science::Medicine The current enhanced permeability and retention (EPR)-based approved nanomedicines have had little impact in terms of prolongation of overall survival in patients with cancer. For example, the two Phase III trials comparing Doxil®, the first nanomedicine approved by the US Food and Drug Administration, with free doxorubicin did not find an actual translation of the EPR effect into a statistically significant increase in overall survival but did show less cardiotoxicity. In the current work, we used a two-factor factorial experimental design with intraperitoneal versus intravenous delivery and nanomedicine versus free drug as factors to test our hypothesis that regional (intraperitoneal) delivery of nanomedicine may better increase survival when compared with systemic delivery. In this study, we demonstrate that bypassing, rather than exploiting, the EPR effect via intraperitoneal delivery of nanomedicine harboring a sustained-release function demonstrates dual pharmacokinetic advantages, producing more efficient tumor control and suppressing the expression of stemness markers, epithelial-mesenchymal transition, angiogenesis signals, and multidrug resistance in the tumor microenvironment. Metastases to vital organs (eg, lung, liver, and lymphatic system) are also better controlled by intraperitoneal delivery of nanomedicine than by standard systemic delivery of the corresponding free drug. Moreover, the intraperitoneal delivery of nanomedicine has the potential to replace hyperthermic intraperitoneal chemotherapy because it shows equal efficacy and lower toxicity. In terms of efficacy, exploiting the EPR effect may not be the best approach for developing a nanomedicine. Because intraperitoneal chemotherapy is a type of regional chemotherapy, the pharmaceutical industry might consider the regional delivery of nanomedicine as a valid alternative pathway to develop their nanomedicine(s) with the goal of better tumor control in the future. Published version 2015-05-20T04:34:11Z 2019-12-06T22:31:14Z 2015-05-20T04:34:11Z 2019-12-06T22:31:14Z 2015 2015 Journal Article Shen, Y. A., Shyu, I. L., Lu, M., He, C. L., Hsu, Y. M., Liang, H. F., et al. (2015). Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control. International journal of nanomedicine, 2485-2502. 1178-2013 https://hdl.handle.net/10356/107443 http://hdl.handle.net/10220/25625 10.2147/IJN.S78321 25848266 en International journal of nanomedicine © 2015 Shen et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License. The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. Permissions beyond the scope of the License are administered by Dove Medical Press Limited. Information on how to request permission may be found at: http://www.dovepress.com/permissions.php 18 p. application/pdf |
| spellingShingle | DRNTU::Science::Medicine Shen, Yao An Shyu, Ing Luen Lu, Maggie He, Chun Lin Hsu, Yen Mei Liang, Hsiang Fa Liu, Chih Peng Liu, Ren Shyan Shen, Biing Jiun Wei, Yau Huei Chuang, Chi Mu Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control |
| title | Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control |
| title_full | Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control |
| title_fullStr | Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control |
| title_full_unstemmed | Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control |
| title_short | Bypassing the EPR effect with a nanomedicine harboring a sustained-release function allows better tumor control |
| title_sort | bypassing the epr effect with a nanomedicine harboring a sustained release function allows better tumor control |
| topic | DRNTU::Science::Medicine |
| url | https://hdl.handle.net/10356/107443 http://hdl.handle.net/10220/25625 |
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