Novel reduction-sensitive micelles for triggered intracellular drug release.

Abstract Novel reduction-sensitive micelles based on poly(ethylene oxide)- b -poly( N -methacryloyl- N ′-( t -butyloxycarbonyl)cystamine) (PEO- b -PMABC) diblock copolymers were developed and applied for triggered intracellular drug release. PEO- b -PMABC block copolymers were synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization of MABC with dithioester-capped PEO as macroRAFT agent. Gel permeation chromatography (GPC) and 1 H NMR analysis showed that the copolymers have controlled compositions and molecular weights, indicating the living nature of polymerization. These copolymers were self-assembled into micelles. The physicochemical characteristics and reduction-sensitivity of the resultant micelles were investigated by fluorescence measurement, transmission electron microscopy (TEM), and dynamic light scattering (DLS). The results showed that PEO- b -PMABC micelles are stable at normal physiologic condition but readily cleaved into free copolymers under reducing environment. In vitro release of doxorubicin (DOX) and cell experiments showed that the drug-loaded PEO- b -PMABC micelles accomplished much faster drug release under reducing condition and higher anticancer efficacy as compared to the control without reduction-sensitivity, indicating great potential of PEO- b -PMABC micelles for efficient intracellular drug delivery.