Highly stable semiconducting polymer nanoparticles for multi-responsive chemo/photothermal combined cancer therapy

Rationale: Structural stability and size controllability are critical issues to semiconducting polymer nanoparticles (SPNs), which currently show great potential for theranostic applications. Methods: Herein, multi-responsive semiconducting polymer semi-interpenetrating nanoparticles (PDPP3T@PNIPAMAA IPNs) with highly stable structure and uniform size have been successfully designed by semi-interpenetrating technique. Results: It is proposed for the first time that PDPP3T@PNIPAMAA IPNs were prepared with "reinforced concrete" particle structure, which is even resistant to organic solvent such as ethanol and THF. By adjusting the polymerization time, the obtained PDPP3T@PNIPAMAA IPNs exhibit uniform and controllable particle size with extremely low polydispersity index (~0.037) at 1 h of reaction time. The presence of pH/light/GSH multi-responsive semi-interpenetrating network in PDPP3T@PNIPAMAA IPNs dramatically increase their drug loading efficiency (92.64%), which is significantly higher than previously reported comparable SPNs-based drug delivery systems. Additionally, PDPP3T@PNIPAMAA-DOX IPNs further provide improved therapeutic efficacy by the combination of chemotherapy and photothermal therapy with controllably regulated release of doxorubicin (DOX). In vitro and in vivo results indicate that PDPP3T@PNIPAMAA-DOX IPNs are able to release drugs at controlled rate by pH/light/GSH regulation and offer PAI-guided chemo/photothermal combined therapy with excellent therapeutic efficacy. Conclusions: The semi-interpenetrating network method may be generally extended for the preparation of a wide range of organic polymer nanoparticles to achieve ultrahigh structural stability, precise particle size controllability and excellent drug loading capacity.