A universal nanoreactor triggering butterfly effect for encouraging Fenton/Fenton-like reactions and chemodynamic...

Fenton/Fenton-like reaction induced chemical dynamic therapy (CDT) has been widely recognized in tumor therapy. Due to the low efficiency of conversion from high-valent metal ions (M⁽ⁿ⁺¹⁾⁺) to low-valent ions (Mⁿ⁺) in the Fenton/Fenton-like catalytic process, enhancing the conversion efficiency safely and effectively would create a great opportunity for the clinical application of CDT. In the study, a universal nanoreactor (NR) consisting of liposome (Lip), tumor cell membrane (CM), and bis(2,4,5-trichloro-6-carboxyphenyl) oxalate (CPPO) is developed to tackle this challenge. The CPPO was first discovered to decompose under weak acidity and H₂O₂ conditions to generate carboxylic acids (R'COOH) and alcohols (R'OH) with reducibility, which will reduce M⁽ⁿ⁺¹⁾⁺ to Mⁿ⁺ and magnify the effect of CDT. Furthermore, glucose oxidase (GOx) was introduced to decompose glucose in tumor and generate H₂O₂ and glucose acid, which promote the degradation of CPPO, further strengthening the efficiency of CDT, leading to a butterfly effect. This demonstrated that the butterfly effect triggered by NR and GOx encourages Fenton/Fenton-like reactions of Fe₃O₄ and MoS₂, thereby enhancing the tumor inhibition effect. The strategy of combining GOx and CPPO to strengthen the Fenton/Fenton-like reaction is a universal strategy, which provides a new and interesting perspective for CPPO in the application of CDT, reflecting the exquisite integration of Fenton chemistry and catalytic medicine.