Dual-targeting dual-action platinum(IV) platform for enhanced anticancer activity and reduced nephrotoxicity
A novel and highly efficient dual‐targeting platform was designed to ensure targeted in vivo delivery of dual‐action PtIV prodrugs. The dual targeting was established by liposomal encapsulation of PtIV complexes, thereby utilizing the enhanced permeability and retention (EPR) effect as the first sta...
| Main Authors: | , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2020
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| Online Access: | https://hdl.handle.net/10356/144107 |
| _version_ | 1826121799195164672 |
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| author | Babak, Maria V. Zhi, Yang Czarny, Bertrand Toh, Tan Boon Hooi, Lissa Chow, Edward Kai-Hua Ang, Wee Han Gibson, Dan Pastorin, Giorgia |
| author2 | School of Materials Science and Engineering |
| author_facet | School of Materials Science and Engineering Babak, Maria V. Zhi, Yang Czarny, Bertrand Toh, Tan Boon Hooi, Lissa Chow, Edward Kai-Hua Ang, Wee Han Gibson, Dan Pastorin, Giorgia |
| author_sort | Babak, Maria V. |
| collection | NTU |
| description | A novel and highly efficient dual‐targeting platform was designed to ensure targeted in vivo delivery of dual‐action PtIV prodrugs. The dual targeting was established by liposomal encapsulation of PtIV complexes, thereby utilizing the enhanced permeability and retention (EPR) effect as the first stage of targeting to attain a high accumulation of the drug‐loaded liposomes in the tumor. After the release of the PtIV prodrug inside cancer cells, a second stage of targeting directed a portion of the PtIV prodrugs to the mitochondria. Upon intracellular reduction, these PtIV prodrugs released two bioactive molecules, acting both on the mitochondrial and on the nuclear DNA. Our PtIV system showed excellent activity in vitro and in vivo, characterized by a cytotoxicity in a low micromolar range and complete tumor remission, respectively. Notably, marked in vivo activity was accompanied by reduced kidney toxicity, highlighting the unique therapeutic potential of our novel dual‐targeting dual‐action platform. |
| first_indexed | 2024-10-01T05:38:04Z |
| format | Journal Article |
| id | ntu-10356/144107 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T05:38:04Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1441072020-11-01T05:21:20Z Dual-targeting dual-action platinum(IV) platform for enhanced anticancer activity and reduced nephrotoxicity Babak, Maria V. Zhi, Yang Czarny, Bertrand Toh, Tan Boon Hooi, Lissa Chow, Edward Kai-Hua Ang, Wee Han Gibson, Dan Pastorin, Giorgia School of Materials Science and Engineering Lee Kong Chian School of Medicine (LKCMedicine) Science::Medicine Antitumor Agents Drug Discovery A novel and highly efficient dual‐targeting platform was designed to ensure targeted in vivo delivery of dual‐action PtIV prodrugs. The dual targeting was established by liposomal encapsulation of PtIV complexes, thereby utilizing the enhanced permeability and retention (EPR) effect as the first stage of targeting to attain a high accumulation of the drug‐loaded liposomes in the tumor. After the release of the PtIV prodrug inside cancer cells, a second stage of targeting directed a portion of the PtIV prodrugs to the mitochondria. Upon intracellular reduction, these PtIV prodrugs released two bioactive molecules, acting both on the mitochondrial and on the nuclear DNA. Our PtIV system showed excellent activity in vitro and in vivo, characterized by a cytotoxicity in a low micromolar range and complete tumor remission, respectively. Notably, marked in vivo activity was accompanied by reduced kidney toxicity, highlighting the unique therapeutic potential of our novel dual‐targeting dual‐action platform. Ministry of Education (MOE) Accepted version G.P. acknowledges the National University of Singapore (NUS) for financial support (grant C-141-000-097-001). W.H.A. acknowledges the Ministry of Education Singapore (MOE) for financial support (grant R143000680114). D.G acknowledges the support of the Israel Science Foundation (grant 1611/14) and the support of the Alex Grass Center for Drug Design and Synthesis.Y.Z. acknowledges the Depart- ment of Pharmacy (NUS) and Hebrew University of Jerusa- lem (HUJ) for the research scholarship for ajoint PhD degree.M.V.B.acknowledges E. Fasolko and T. Hajsz for generating the artwork. 2020-10-13T09:06:38Z 2020-10-13T09:06:38Z 2019 Journal Article Babak, M. V., Zhi, Y., Czarny, B., Toh, T. B., Hooi, L., Chow, E. K.-H., . . . Pastorin, G. (2019). Dual‐targeting dual‐action platinum(IV) platform for enhanced anticancer activity and reduced nephrotoxicity. Angewandte Chemie International Edition, 58(24), 8109-8114. doi:10.1002/anie.201903112 1433-7851 https://hdl.handle.net/10356/144107 10.1002/anie.201903112 30945417 24 58 8109 8114 en Angewandte Chemie International Edition This is the accepted version of the following article: Babak, M. V., Zhi, Y., Czarny, B., Toh, T. B., Hooi, L., Chow, E. K.-H., . . . Pastorin, G. (2019). Dual‐targeting dual‐action platinum(IV) platform for enhanced anticancer activity and reduced nephrotoxicity. Angewandte Chemie International Edition, 58(24), 8109-8114. doi:10.1002/anie.201903112, which has been published in final form at http://doi.org/10.1002/anie.201903112. This article may be used for non-commercial purposes in accordance with the Wiley Self-Archiving Policy [https://authorservices.wiley.com/authorresources/Journal-Authors/licensing/self-archiving.html]. application/pdf |
| spellingShingle | Science::Medicine Antitumor Agents Drug Discovery Babak, Maria V. Zhi, Yang Czarny, Bertrand Toh, Tan Boon Hooi, Lissa Chow, Edward Kai-Hua Ang, Wee Han Gibson, Dan Pastorin, Giorgia Dual-targeting dual-action platinum(IV) platform for enhanced anticancer activity and reduced nephrotoxicity |
| title | Dual-targeting dual-action platinum(IV) platform for enhanced anticancer activity and reduced nephrotoxicity |
| title_full | Dual-targeting dual-action platinum(IV) platform for enhanced anticancer activity and reduced nephrotoxicity |
| title_fullStr | Dual-targeting dual-action platinum(IV) platform for enhanced anticancer activity and reduced nephrotoxicity |
| title_full_unstemmed | Dual-targeting dual-action platinum(IV) platform for enhanced anticancer activity and reduced nephrotoxicity |
| title_short | Dual-targeting dual-action platinum(IV) platform for enhanced anticancer activity and reduced nephrotoxicity |
| title_sort | dual targeting dual action platinum iv platform for enhanced anticancer activity and reduced nephrotoxicity |
| topic | Science::Medicine Antitumor Agents Drug Discovery |
| url | https://hdl.handle.net/10356/144107 |
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