Well‐Defined Polymer–Paclitaxel Prodrugs by a Grafting‐from‐Drug Approach |
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Authors: | Benoit Louage Dr Lutz Nuhn Dr Martijn D P Risseeuw Nane Vanparijs Ruben De Coen Izet Karalic Prof Dr Serge Van Calenbergh Prof Dr Bruno G De Geest |
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Institution: | 1. Biopharmaceutical Technology Unit, Department of Pharmaceutics, Ghent University, Ghent, Belgium;2. Laboratory of Medicinal Chemistry, Department of Pharmaceutics, Ghent University, Ghent, Belgium |
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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. |
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Keywords: | cancer nanotechnology paclitaxel prodrugs RAFT polymerization |
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