A magnetic nanoreactor with microenvironment regulation capability for targeted and enhanced tumor chemodynamic therapy

Chemodynamic therapy (CDT) is a promising method of using nanomedicines to induce Fenton or Fenton-like reactions for tumor specific treatment. However, the insufficient tumor targeting of nanomedicines as well as high expression of glutathione (GSH) and low concentration of hydrogen peroxide (H2O2) within tumor cells significantly limit the effect of CDT. Here, a magnetic nanoreactor CoFe2O4@PALA-g-mPEG/JUG (CFO@PA-P/J) with tumor microenvironment regulation capability was fabricated for highly efficient CDT. Juglone (JUG) loaded branched polymer based on poly(alpha-lipoic acid) (PA) was decorated on the surface of magnetic CFO nanoparticle to produce CFO@PA-P/J, which can selectively accumulate in tumor sites in the presence of external magnetic field. Besides, the PA component that rich in disulfide bonds can react with GSH in situ, reducing the antioxidant defense ability of tumor cells. Moreover, JUG can promote the generation of intracellular H2O2, providing more sufficient substrates for CDT. Notably, the above microenvironment regulation by CFO@PA-P/J significantly enhances oxidative stress and induces strong apoptosis in vivo, ultimately achieving highly efficient tumor suppression based on CDT.