Enhanced tumor therapy via GSH-depleting and MRI-guided ZIF-67@Mn-PDA nanoagent for synergistic chemodynamic/photothermal treatment.

Chemodynamic therapy (CDT) faces significant challenges within the complex tumor microenvironment (TME), particularly due to glutathione(GSH)-mediated scavenging of reactive oxygen species (ROS) and insufficient endogenous H2O2. To address this, we developed a multifunctional nanoagent, ZIF-67@Mn-PDA, by integrating manganese-doped polydopamine (Mn-PDA) with zeolitic imidazolate framework-67 (ZIF-67). This composite leverages the high Fenton-like activity of ZIF-67-derived Co²⁺ and the GSH-consumption capability of Mn-PDA, which also releases Mn²⁺ for T₁-weighted magnetic resonance imaging (MRI). The Mn-PDA shell significantly enhances photothermal conversion efficiency (24.39 %) under 808 nm laser irradiation, accelerating Fenton-like kinetics and enabling combined photothermal therapy (PTT). In vitro and in vivo studies confirmed effective GSH depletion, synergistic CDT/PTT efficacy, and MRI-guided tumor inhibition. This work offers a promising TME-responsive nanoplatform for precise and effective tumor theranostics via cascaded actions.