Starvation-assisted and photothermal-thriving combined chemo/chemodynamic cancer therapy with PT/MR bimodal imaging

Abstract

Chemodynamic therapy (CDT) reflects a novel reactive oxygen species (ROS)-related cancer therapeutic approach. However, CDT monotherapy is often limited by weak efficacy and insufficient endogenous H₂O₂. Herein, a multifunctional combined bioreactor (MnFe-LDH/MTX@GOx@Ta, MMGT) relying on MnFe-layered double hydroxide (MnFe-LDH) loaded with methotrexate (MTX) and coated with glucose oxidase (GOx)/tannin acid (Ta) is established for applications in H₂O₂ self-supply and photothermal enhanced chemo/chemodynamic combined therapy along with photothermal (PT) /magnetic resonance (MR) dual-modality imaging ability for cancer treatment. Once internalized into tumor cells, MMGT achieves starvation therapy by catalyzing the oxidation of glucose with GOx, accompanied by the regeneration of H₂O₂, enabling a Fenton-like reaction to accomplish GOx catalytic amplified CDT. Moreover, MMGT manifests significant tumor-killing ability through improved CDT performance with outstanding photothermal conversion efficiency (η = 52.2%) under 808 nm laser irradiation. In addition, the release of Mn²⁺ from MnFe-LDH in a solid tumor can significantly enhance T₁-contrast MR imaging signals. Combined with MnFe-LDH-induced PT imaging under 808 nm laser irradiation, a dual-modality imaging directed theranostic nanoplatform has been developed. The present study provides a new strategy to design H₂O₂ self-supply and ROS evolving NIR light-absorption theranostic nanoagent for highly efficient and combined chemo/chemodynamic cancer treatment.