Cyclodextrin polyrotaxane based self oxygen supplying nanoparticles for enhancing the sonodynamic therapy mammary cancer performance with a "one-stone-two-birds" strategy.

Sonodynamic therapy (SDT) is a novel anti-tumor approach that offers the advantages of deep penetration, high therapeutic efficacy, and minimal damage to normal tissues. However, the organic sonosensitizers tetraphenylporphyrin can inhibit the production of reactive oxygen species (ROS) due to the intermolecular π-π stacking effect, resulting in a poor SDT effect. SDT utilizing oxygen-dependent sonosensitizers are frequently limited by the hypoxic microenvironment characteristic of solid tumors. Herein, we have successfully developed an enhanced SDT self oxygen supplying delivery system based on cyclodextrin polyrotaxane to inhibit the π-π stacking effect between tetraphenylporphyrin molecules and improve the hypoxic microenvironment. A "one-stone-two-birds" strategy was proposed. On one hand, the spatial effect of cyclodextrin and polyrotaxane was utilized to enhance the yield of ROS from the sonosensitizers agent porphyrin. On the other hand, the GOx and manganese dioxide nanozyme were loaded onto polyrotaxane through electrostatic adsorption, enabling the reversal of hypoxic environment at the tumor site through a cascade reaction. Ultimately, the prepared polyrotaxane nanoparticles, combined with targeted accumulation to enhance SDT efficacy and starvation therapy, resulted in a 76 % suppression of tumor growth. This study develops an innovative approach to enhance SDT performance of tetraphenylporphyrin via cyclodextrin polyrotaxane spatial effects, while offering a novel strategy to alleviate tumor hypoxia.