Sono-promoted piezocatalysis and low-dose drug penetration for personalized therapy via tumor organoids.

ABSTRACT

Chemotherapy is a widely used cancer treatment, however, it can have notable side effects owing to the high-doses of drugs administered. Sonodynamic therapy (SDT) induced by sonosensitizers has emerged as a promising approach to treat cancer, however, there is limited research evaluating its therapeutic effects on human tumors. In this study, we introduced a dual therapy that combines low-dose chemotherapeutic drugs with enhanced sonodynamic therapy, utilizing barium titanate (BaTiO3, BTO) nanoparticles (NPs) as sonosensitizers to treat tumor organoids. We demonstrated that ultrasound could improve the cellular uptake of chemotherapy drugs, while the chemotherapeutic effect of the drugs made it easier for BTO NPs to enter tumor cells, and the dual therapy synergistically inhibited tumor cell viability. Moreover, different patient-derived tumor organoids exhibited different sensitivities to this therapy, highlighting the potential to evaluate individual responses to combination therapies prior to clinical intervention. Furthermore, this dual therapy exhibited therapeutic effects equivalent to those of high-dose chemotherapy drugs on drug-resistant tumor organoids and showed the potential to enhance the efficacy of killing drug-resistant tumors. In addition, the biosafety of the BTO NPs was successfully verified in live mice via oral administration. This evidence confirms the reliable and safe nature of the dual therapy approach, making it a feasible option for precise and personalized therapy in clinical applications.