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- Title
Well-Defined Polymer-Paclitaxel Prodrugs by a Grafting-from-Drug Approach.
- Authors
Louage, Benoit; Nuhn, Lutz; Risseeuw, Martijn D. P.; Vanparijs, Nane; De Coen, Ruben; Karalic, Izet; Van Calenbergh, Serge; De Geest, Bruno G.
- Abstract
We report on the design of a polymeric prodrug of the anticancer agent paclitaxel (PTX) by a grafting-from-drug approach. A chain transfer agent for reversible addition fragmentation chain transfer (RAFT) polymerization was efficiently and regioselectively linked to the C2′ position of paclitaxel, which is crucial for its bioactivity. Subsequent RAFT polymerization of a hydrophilic monomer yielded well-defined paclitaxel-polymer conjugates with high drug loading, water solubility, and stability. The versatility of this approach was further demonstrated by ω-end post-functionalization with a fluorescent tracer. In vitro experiments showed that these conjugates are readily taken up into endosomes where native PTX is efficiently cleaved off and then reaches its subcellular target. This was confirmed by the cytotoxicity profile of the conjugate, which matches those of commercial PTX formulations based on mere physical encapsulation.
- Subjects
ANTINEOPLASTIC agents; TRANSPLANTATION of organs, tissues, etc.; SOLUBILITY; ANTIBODY-dependent cell cytotoxicity; POLYMERIZATION
- Publication
Angewandte Chemie International Edition, 2016, Vol 55, Issue 39, p11791
- ISSN
1433-7851
- Publication type
Article
- DOI
10.1002/anie.201605892