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|Title:||Dual-targeting dual-action platinum(IV) platform for enhanced anticancer activity and reduced nephrotoxicity||Authors:||Babak, Maria V.
Toh, Tan Boon
Chow, Edward Kai-Hua
Ang, Wee Han
|Keywords:||Science::Medicine||Issue Date:||2019||Source:||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||Journal:||Angewandte Chemie International Edition||Abstract:||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.||URI:||https://hdl.handle.net/10356/144107||ISSN:||1433-7851||DOI:||10.1002/anie.201903112||Rights:||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].||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||LKCMedicine Journal Articles|
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