Interfacial Engineering of Pillararene-Modified Ceria Nanoparticles for Regulable Enhanced Sonodynamic Therapy

Sonodynamic therapy (SDT) has emerged as an advanced technology for treatment of malignant tumors. Many organic and inorganic sonosensitizers have been reported but they still have the respective limitations. Constructing the materials to integrate the superiorities of organic and inorganic sonosensitizers is expected to be a good method to enhance the efficiency of SDT. Herein, we report an intelligent sonosensitizer (TPA–OS⊂CP5@CeO_x), integrating the organic (TPA–OS) and inorganic sonosensitizers (CP5@CeO_x) via host–guest interaction. The modification of carboxyl-pillar[5]arene (CP5) on CeO_x constructs the supramolecular interface by coupling of CP5 and oxygen vacancies. The band gap of CeO_x is reduced and the ratio of Ce⁴⁺/Ce³⁺ is increased to regulate tumor microenvironment. Thus, the SDT performance of CP5@CeO_x can be improved. Furthermore, the synergistic effect of TPA–OS with aggregation-induced emission can further regulate and enhance the SDT efficiency. The cellular experiments demonstrate that TPA–OS⊂CP5@CeO_x exhibits the synergistic therapeutic effect in double organelle of lysosome and mitochondria. The in vivo experiments suggest TPA–OS⊂CP5@CeO_x has imaging-guided enhanced SDT performance to achieve tumor inhibition. This study contributes to the construction of novel intelligent sonosensitizers, indicating that supramolecular interface engineering is promising to realize the customized treatments with minimal side effects.