Redox-responsive long chain supramolecular hyperbranched polymer for controlled drug release

Stimuli-responsiveness in biological body and high drug loading efficiency are two of the prerequisites to conduct controlled drug release of supramolecular hyperbranched polymers (SHPs). Herein, the redox-responsive long chain SHP was constructed by click reaction of AB₂ type macromonomer (MM), which contains thiol and alkynyl groups as well as β-cyclodextrin (β-CD)/Fcrrocene (Fc). A linear cationic polymer with thiol group at one end and β-cyclodextrin at the other end was first synthesized by the combination of reversible addition-fragmentation chain transfer polymerization (RAFT), ring-opening reaction and end group modification. And then, the AB₂-type macromonomer was prepared by the inclusion complexation between β-CD and Fc in aqueous solution. The final SHP was achieved by click reaction of thiol group with alkynyl group under UV irradiation. The polymer structure and supramolecular interaction of MM and SHP were confirmed by¹H nuclear magnetic resonance and 2D NOSEY spectra. The self-assembly of SHP in aqueous solution was further investigated through transmission electron microscopy (TEM) and dynamic light scattering (DLS). Both TEM and DLS results indicated that SHP self-assembled into branched aggregates without external stimuli, and then dissociated and secondly self-assembled into irregular spherical self-assemblies due to the dissociation of β-CD and Fc complexes induced by reducing agent H₂O₂. The SHP self-assemblies possess a high doxorubicin (DOX) loading capacity compared with linear supramolecular polymer self-assemblies. Furthermore, by utilizing the above H₂O₂-tuned self-assembly morphology transition feature, a smart drug delivery behavior was observed through the cumulative release curves of DOX-loaded SHP self-assemblies. The controlled drug release behavior of SHP self-assemblies embedded DOX under pH = 7.4 and 5.0 was deeply studied. The results indicated that H₂O₂ broke the host-guest interaction between β-CD and Fc, leading to a fast release of DOX. Meantime, the dissociation of SHP self-assemblies further self-assembled into small solid micelles. Therefore, the release behavior of DOX-loaded SHP self-assemblies presented the redox-responsive characteristics.