Well-Defined Polymer-Paclitaxel Prodrugs by a Grafting-from-Drug Approach

Louage, Benoit; Nuhn, Lutz; Risseeuw, Martijn D. P.; Vanparijs, Nane; De Coen, Ruben; Karalic, Izet; Van Calenbergh, Serge; De Geest, Bruno G.

doi:10.1002/anie.201605892

Item

ITEM ACTIONSEXPORT

Add to Basket

Local TagsRelease HistoryDetailsSummary

Released

Journal Article

Well-Defined Polymer-Paclitaxel Prodrugs by a Grafting-from-Drug Approach

MPS-Authors

There are no MPG-Authors in the publication available

External Resource

No external resources are shared

Fulltext (restricted access)

There are currently no full texts shared for your IP range.

Fulltext (public)

There are no public fulltexts stored in PuRe

Supplementary Material (public)

There is no public supplementary material available

Citation

Louage, B., Nuhn, L., Risseeuw, M. D. P., Vanparijs, N., De Coen, R., Karalic, I., et al. (2016). Well-Defined Polymer-Paclitaxel Prodrugs by a Grafting-from-Drug Approach. Angewandte Chemie, International Edition, 55(39), 11791-11796. doi:10.1002/anie.201605892.

Cite as: https://hdl.handle.net/21.11116/0000-0005-9ACD-7

Abstract

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.