ROS‐Responsive and Self‐Tumor Curing Methionine Polymer Library Based Nanoparticles with Self‐Accelerated Drug Release and Hydrophobicity/Hydrophilicity Switching Capability for Enhanced Cancer Therapy

Abstract The applications of amino acid‐based polymers are impeded by their limited structure and functions. Herein, a small library of methionine‐based polymers (Met‐P) with programmed structure and reactive oxygen species (ROS)‐responsive properties is developed for tumor therapy. The Met‐P can self‐assemble into sub‐100 nm nanoparticles (NPs) and effectively load anticancer drugs (such as paclitaxel (PTX) (P@Met‐P NPs)) via the nanoprecipitation method. The screened NPs with superior stability and high drug loading are further evaluated in vitro and in vivo. When encountering with ROS, the Met‐P polymers will be oxidized and then switch from a hydrophobic to a hydrophilic state, triggering the rapid and self‐accelerated release of PTX. The in vivo results indicated that the screened P@2Met10 NPs possessed significant anticancer performance and effectively alleviated the side effects of PTX. More interestingly, the blank 2Met10 NPs displayed an obvious self‐tumor inhibiting efficacy. Furthermore, the other Met‐P NPs (such as 2Met8, 4Met8, and 4Met10) are also found to exhibit varied self‐anti‐cancer capabilities. Overall, this ROS‐responsive Met‐P library is a rare anticancer platform with hydrophobic/hydrophilic switching, controlled drug release, and self‐anticancer therapy capability.