Multifunctional nanoparticles for enhanced sonodynamic-chemodynamic immunotherapy with glutathione depletion

Aim: This study aimed to develop a sonodynamic-chemodynamic nanoparticle functioning on glutathione depletion in tumor immunotherapy. Materials & methods: The liposome-encapsulated 2,2-azobis[2-(2-imidazolin-2-yl) propane] dihydrochloride (AIPH) and copper-cysteine nanoparticles, AIPH/Cu-Cys@Lipo, were synthesized with a one-pot method. 4T1 cells were injected into female BALB/c mice for modeling. Results: AIPH/Cu-Cys@Lipo was well synthesized. It generated alkyl radicals upon ultrasound stimulation. AIPH/Cu-Cys@Lipo promoted the generation of -OH via a Fenton-like reaction. Both in vitro and in vivo experiments verified that AIPH/Cu-Cys@Lipo significantly inhibited tumor development by decreasing mitochondrial membrane potential, activating CD4⁺ and CD8⁺ T cells and promoting the expression of IL-2 and TNF-α. Conclusion: AIPH/Cu-Cys@Lipo provides high-quality strategies for safe and effective tumor immunotherapy.