Reduction-Sensitive Polymeric Micelles for Intracellular Doxorubicin Delivery

Abstract

The hazard of cancer is continuously increasing with age, Doxorubicin (DOX) encapsulated by liposomes as an effective formulation is widely used to treat malignancies. To avoid the cardiotoxicity of DOX and increase the half-life and targeting of liposomal drugs, redox-sensitive nanoparticle that improve the delivery of therapeutics to target tissue have become an extensive choice of medical treatment. In this work, we synthesised a kind of redox-sensitive product, PEG-redox-DOX micelles which were made of PEG-SS-COOH coupled with DOX by a reduction-sensitive disulfide bond. This micellar system has a mean diameter of 60nm with acceptable distribution (PDI=0.81) and remained unchanged in phate buffered saline (PBS, pH=7.4) for 24 hours. However, the disulfide bond between DOX and hydrophilic PEG broke readily in the presence of 10 mM DTT imitating intracellular condition. The micelle released more than 75% DOX within 48h at 10 mM DTT, whereas only 12% DOX were released from prodrug at 0 mM DTT. These results suggest that PEG-redox-DOX has expectable efficiency of drug-loading and release. Nowadays, redox-sensitive micelles are more and more taken into considered, demonstrating its developmental potential in cancer therapy categories by providing a new search direction.