FeOCl Nanodots and Doxorubicin Co-loaded Polymer Nanoparticles for Glutathione/pH-responsive Chemodynamic Therapy/Chemotherapy of Tumors

Graphical FeOCl nanodots were prepared by a ball-milling method and used as novel Fenton agents. Glutathione/pH dual-responsive polymer nanoparticles were synthesized by co-polymerization of acrylic acid and 3-methacrylamido dopamine with a cross-linker containing disulfide bonds, which can load FeOCl nanodots and doxorubicin to form a multifunctional nanoplatform for efficient chemodynamic therapy/chemotherapy. Chemodynamic therapy (CDT) based on the Fenton reaction has been considered as a promising solution for the treatment of tumors. However, the limited therapeutic efficacy and lack of responsive release of Fenton agents still hinder the further application of CDT. To this end, we designed a disulfide bond (−S−S−) cross-linked polymer nanoparticles (poly(AA-co-DMA), PAD) to load FeOCl nanodots (FeOCl NDs) and doxorubicin (DOX) with the surface coating of bovine serum albumin (BSA) to prepare glutathione (GSH)/pH-responsive PAD-FeOCl/DOX@BSA nanoparticles (PFDB). In the tumor microenvironment (TME) with abundant GSH and acidic pH, the −S−S− bond in PFDB can be reduced and the linkage between the polymer chains is broken down, which facilitates the controlled release of FeOCl NDs and DOX. Both in vitro and in vivo experimental results showed that PFDB can serve as a GSH/pH-responsive nanoagent for the effective killing of 4T1 tumor cells by combined CDT/chemotherapy. This study provides a promising TME-responsive nanoagent with dual therapeutic modes for the effective treatment of tumors.