A novel manganese dioxide-based drug delivery strategy via in situ coating γ-polyglutamic acid/cisplatin for intelligent anticancer therapy.

Cisplatin (CDDP) is one of the most frequently used chemotherapeutic drugs due to its broad-spectrum and potent antitumor activity. Unfortunately, inactivation due to glutathione (GSH) substances and insufficient cellular uptake of CDDP greatly hinder its clinical applications. Herein, manganese dioxide (MnO 2 ) was reported as an efficient glutathione (GSH) consumption material for promoting the accumulation and preventing premature leakage of CDDP in tumor cells. In this work, γ-polyglutamic acid/cisplatin (PGA/CDDP) conjugates and PGA/CDDP nanoparticles (NPs) were respectively constructed via the ligand exchange reaction and electrostatic interaction. Furthermore, PGA/CDDP NPs were in situ coated with MnO 2 (PGA/CDDP@MnO 2 NPs) through the redox reaction of the residual carboxyl group (-COOH) and potassium permanganate (KMnO 4 ). As a result, the PGA/CDDP@MnO 2 NPs achieved a satisfactory drug-loading efficiency ( ca. 37.26%) and multi-responsive controlled drug release. Remarkably, the MnO 2 shells exhibited excellent performance for efficient glutathione (GSH) consumption and significantly enhanced the killing effect ( ca. 2-3 times) in human lung cancer cells (A549) compared with pure CDDP. Moreover, it was observed that PGA/CDDP@MnO 2 NPs could also inhibit the migration and invasion of A549 cells. Overall, these remarkable performances of PGA/CDDP@MnO 2 NPs make MnO 2 promising for controlled drug release and intelligent anticancer therapy.