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.

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.