The synthesis of protein decorated and functional star polymers designed for the delivery of Doxorubicin is described. Poly(oligoethylene glycol) methyl ether acrylate was polymerized via reversible addition fragmentation transfer polymerization (RAFT), and then chain extended in the presence of both a cross-linker and comonomer vinyl benzaldehyde, yielding monodisperse star polymers with an aldehyde functional core with a size around 20 nm. The presence of allyl and alkyne groups on the surface of star polymers was exploited to attach different functional protein via thiol-ene or azide alkyne. The bioconjugation yield was determined by gel electrophoresis. The presence of aldehyde groups in the core was exploited to attach doxorubicin via a condensation reaction. The drug loading was controlled by the amount of vinyl benzaldehyde incorporated in the care. These star polymers can carry until 28wt-% in drug without any significant change in their stability. The release of doxorubicin was studied at pH =5.5 and 7.4; conditions representative of endosomal and extra cellular conditions. At the lower pH, doxorubicin was released efficiently from the star, in contrast, at a higher pH 7.4, the conjugates only released doxorubicin slowly. In-vitro studies revealed that the star polymers (no drug conjugated) were non-cytotoxic. The doxorubicin-conjugated star polymers had a level of cytotoxicity comparable to that found for free doxorubicin after three days. Confocal microscopy and flow cytometry studies confirmed efficient cell-uptake of the star polymers and subsequent delivery of the doxorubicin to the cell nucleus.

Synthesis of protein decorated, functional core, star polymers via RAFT polymerization for doxorubicin delivery and active targeting

244th National Meeting (2012)

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