GSH/pH dual-activated POM@MOF for tumor cell-specific synergistic photothermal and chemodynamic therapy

Photothermal therapy (PTT) is emerging as a promising therapeutic approach for tumor treatment. However, the low therapeutic effect of photothermal agents due to their non-specificity and the monotherapy approach remains challenging for further applications. Herein, tumor microenvironment (TME) specifically responsive POM@MOF composites with sequential activation properties were constructed by encapsulating POMs (PMo₁₂, short for H₃PMo₁₂O₄₀) into metal organic framework (MIL-101) carriers for synergistic PTT/chemodynamic therapy (CDT) treatment. PMo₁₂@MIL-101 releases PMo₁₂ and Fe³⁺ under acidic TME conditions, which are subsequently converted into reduced PMo₁₂ and Fe²⁺ by GSH in the TME. PMo₁₂ in its reduced state exhibits excellent photothermal conversion efficiency (47.03%) under near-infrared laser irradiation, which boosts the CDT effects by accelerating the reaction between H₂O₂ and Fe²⁺ and producing more ˙OH radicals. The resulting PTT/CDT synergistic therapeutic effects are highly dependent on the pH value and GSH concentration in the TME, and exhibit a strong inhibition of HepG2 cell proliferation compared to monotherapy.