Synergistic effects of doxorubicin loaded silk fibroin nanoparticles and Cu-TiO2 nanoparticles for local chemo-sonodynamic therapy against breast cancer

A promising new approach to mitigate the adverse effects of chemotherapeutic drugs on healthy tissues involves combining sonodynamic therapy with topical chemotherapy to enhance the therapeutic efficacy of anticancer drugs. In this study, we introduce a multi-functional in situ chitosan hydrogel (CS) containing silk fibroin nanoparticles (SFNPs) loaded with doxorubicin (DOXSFNPs) and CuO/TiO2 nanoparticles (CTNPs) for combination therapy. The developed DOXSFNPs exhibited a size of 257 ± 6 nm, a zeta potential of −14.3 ± 1.8 mV, and a high loading capacity of 12.38 ± 1.73 %. The pH-dependent controlled release of DOX from DOXSF2/CS2 was observed to be more pronounced than that from DOX/CS2. MTT results indicated dose-dependent toxicity of CT/CS2 in response to ultrasaound radiation (US). Our findings revealed a 1.83-fold increase in reactive oxygen species (ROS) production with therapy, with the IC50 of CT3-DOXSF2/CS2-US showing a 58 % reduction compared to CT3/DOXSF2/CS2. In vivo outcomes and histopathological staining demonstrated that the CT3/DOXSF2/CS2-US treatment group exhibited the highest tumor growth inhibition rate, reaching approximately 83.65 %. These findings underscore the potential of this approach in minimizing the adverse effects of chemotherapy while maximizing therapeutic outcomes, offering a valuable contribution to the field of cancer therapy. [Display omitted]