Dual-Targeting Dual-Action Platinum(IV) Platform for Enhanced Anticancer Activity and Reduced Nephrotoxicity
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:58 |
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| Enthalten in: |
Angewandte Chemie (International ed. in English) - 58(2019), 24 vom: 11. Juni, Seite 8109-8114 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Babak, Maria V [VerfasserIn] |
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| Links: |
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| Themen: |
49DFR088MY |
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| Anmerkungen: |
Date Completed 08.09.2020 Date Revised 08.09.2020 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/anie.201903112 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM295671793 |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Czarny, Bertrand |e verfasserin |4 aut | |
| 700 | 1 | |a Toh, Tan Boon |e verfasserin |4 aut | |
| 700 | 1 | |a Hooi, Lissa |e verfasserin |4 aut | |
| 700 | 1 | |a Chow, Edward Kai-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Ang, Wee Han |e verfasserin |4 aut | |
| 700 | 1 | |a Gibson, Dan |e verfasserin |4 aut | |
| 700 | 1 | |a Pastorin, Giorgia |e verfasserin |4 aut | |
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