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

Abstract

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 (MnO₂) 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 MnO₂ (PGA/CDDP@MnO₂ NPs) through the redox reaction of the residual carboxyl group (–COOH) and potassium permanganate (KMnO₄). As a result, the PGA/CDDP@MnO₂ NPs achieved a satisfactory drug-loading efficiency (ca. 37.26%) and multi-responsive controlled drug release. Remarkably, the MnO₂ 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@MnO₂ NPs could also inhibit the migration and invasion of A549 cells. Overall, these remarkable performances of PGA/CDDP@MnO₂ NPs make MnO₂ promising for controlled drug release and intelligent anticancer therapy.