Oxidation Responsive PEGylated Polyamino Acid Bearing Thioether Pendants for Enhanced Anticancer Drug Delivery.

Abstract

Reactive oxygen species (ROS) in biological tissues are in a state of dynamic balance. However, many diseases such as cancer and inflammation, are accompanied by a long-term increase in ROS. This situation inspires researchers to use ROS-sensitive nanocarriers for a site-specific release of cargo in pathological areas. Polyamino acid materials with good biodegradability, biocompatibility, and regular secondary structure are widely used in the biomedical field. Herein, a new oxidation responsive PEGylated polyamino acid is synthesised for anticancer drug delivery by ring-opening polymerisation of N-carboxyanhydrides bearing thioether pendants. The obtained block copolymer mPEG-b-PMLG self-assembles into spherical nanoparticles (NPs) in water with diameter ≈68.3nm. NMR measurement demonstrated that the hydrophobic thioether pendants in the NPs can be selectively oxidised to hydrophilic sulfoxide groups by H2 O2 , which will lead to the disassociation of NPs. In vitro drug release results indicated that the encapsulated Nile red is selectively released in the trigger of 10mM H2 O2 in PBS. Finally, anticancer drug doxorubicin (DOX) is encapsulated to the NPs, and the obtained NPs/DOX exhibits an improved antitumor efficacy in 4T1 tumour-bearing mice and lower cardiotoxicity than free DOX. These results indicates that the mPEG-b-PMLG NPs are promising for anticancer drug delivery.