Glutathione-Triggered Au@MnO₂ For Dual-Imaging-Guided Photothemal-Enhanced Chemodynamic Therapy

Photothermal therapy uses near-infrared absorbing reagents to convert the light energy of laser light into heat energy to kill tumors,while chemodynamic therapy uses Fenton or Fenton-like reactions to convert highly expressed H₂O₂ in the tumors into highly toxic hydroxyl radicals?·OH?to kill the tumor.However,the high expression of heat shock protein and the low catalytic performance of Fenton reagent limit the effectiveness of photothermal therapy and chemodynamic therapy,respectively.In addition,nanomedicines are easily trapped in normal tissues in vivo,causing signal interference and side effects of treatment.Based on this,we have designed and developed the Au@MnO₂ smart reagent triggered by glutathione?GSH?.This reagent can only have imaging and therapeutic effects under the trigger of high-expression GSH in tumors,improve the diagnostic accuracy and reduce the side effects of treatment.In addition,the photothemal-enhanced chemodynamic therapy strategy also greatly improved the treatment effect.Details as follows:Firstly,the synthesis of Au@MnO₂ smart reagent and in vitro triggering properties were explored.The homogeneous and stable Au@MnO₂ nanoparticles were prepared by simple seed coating method.The nanoparticles have low photothermal,photoacoustic,and T₁-weighted MR imaging performance in an environment without GSH.However,after the nanoparticles encounter GSH,MnO₂ will be reduced to Mn²⁺,and Au will also be self-assembled by GSH.The generated Mn²⁺can be used for MR imaging and chemodynamic therapy;self-assembled Au used for photoacoustic imaging and photothermal therapy.More importantly,under the photothermal conditions of Au assembly,Mn²⁺showed stronger Fenton-like catalytic performance.Secondly,explore the biocompatibility and in vivo triggering performance of Au@MnO₂ smart reagent.The MTT and hemolysis experiments proved that the Au@MnO₂ smart reagent has low cytotoxicity and good biocompatibility.Then,contrast experiments of intra-tumor and subcutaneous photoacoustic and MR imaging proved that the smart agent can be effectively triggered in tumors.Finally,the intravenous injection experiment found that after 8 hours of administration,the smart agent has the strongest MRI and photoacoustic contrast at the tumor site.At the same time,the tissue distribution of the smart reagent also proved that there was the maximum tumor enrichment after 8 h of injection.These results again proved that the smart reagent could be effectively activated at the tumor site.Thirdly,under the guidance of photoacoustic and MR imaging,4T1tumor-bearing mice were used as models to treat with Au@MnO₂ smart reagent.Finally,the photothemal-enhanced chemodynamic therapy group had the best therapeutic effect,further proving that Au@MnO₂ nanoparticles had good photothemal-enhanced chemodynamic therapy effect.