Facile Synthesis of Fe₃O₄@Au/PPy-DOX Nanoplatform with Enhanced Glutathione Depletion and Controllable Drug Delivery for Enhanced Cancer Therapeutic Efficacy

Abstract

The complex physiological environment and inherent self-healing function of tumors make it difficult to eliminate malignant tumors by single therapy. In order to enhance the efficacy of antitumor therapy, it is significant and challenging to realize multi-mode combination therapy by utilizing/improving the adverse factors of the tumor microenvironment (TME). In this study, a novel Fe3O4@Au/PPy nanoplatform loaded with a chemotherapy drug (DOX) and responsive to TME, near-infrared (NIR) laser and magnetic field was designed for the combination enhancement of eliminating the tumor. The Fe2+ released at the low pH in TME can react with endogenous H2O2 to induce toxic hydroxyl radicals (·OH) for chemodynamic therapy (CDT). At the same time, the generated Fe3+ could deplete overexpressed glutathione (GSH) at the tumor site to prevent reactive oxygen species (ROS) from being restored while producing Fe2+ for CDT. The designed Fe3O4@Au/PPy nanoplatform had high photothermal (PT) conversion efficiency and photodynamic therapy (PDT) performance under NIR light excitation, which can promote CDT efficiency and produce more toxic ROS. To maximize the cancer-killing efficiency, the nanoplatform can be successfully loaded with the chemotherapeutic drug DOX, which can be efficiently released under NIR excitation and induction of slight acidity at the tumor site. In addition, the nanoplatform also possessed high saturation magnetization (20 emu/g), indicating a potential magnetic targeting function. In vivo and in vitro results identified that the Fe3O4@Au/PPy-DOX nanoplatform had good biocompatibility and magnetic-targeted synergetic CDT/PDT/PTT/chemotherapy antitumor effects, which were much better than those of the corresponding mono/bi/tri-therapies. This work provides a new approach for designing intelligent TME-mediated nanoplatforms for synergistically enhancing tumor therapy.

Keywords

• Fe₃O₄@Au/PPy nanoplatform
• tumor microenvironment
• glutathione-depleting
• multimodal cancer therapy
• DOX