Nanostructured Lipid Carriers Containing Acridine Derivatives in the Application of Sonodynamic Therapy for the Treatment of Breast Cancer

Through sonosensitizing agent activation, sonodynamic therapy (SDT) generates an imbalance of reactive oxygen species (ROS) that is potentially damaging to target cells. Acridine derivatives (AD), such as AMTAC compounds (01, 02, 18, 22), present properties of sonosensitizing agents for use in SDT. This work aims to formulate and characterize nanostructured lipid carriers (NLC) containing AD for the application of SDT as a low-invasive breast cancer (BC) treatment. DLS, ELS, SOSG assay, MTT assay, <i>in vitro</i> release study, and <i>in vivo</i> efficacy techniques were applied. DLS and ELS showed a size range of 107.03 to 119.96 nm, zeta potential of -14.31 to -4.12 mV, and a polydispersity index of 0.17 to 0.26. The SOSG assay demonstrated that AMTAC 02 generated the highest amount of ROS (282%). The combination of SOSG and the MTT results, which showed cell viability <40% for all the compounds, resulted in the selection of AMTAC 02 to proceed with further studies. The NLC+AMTAC 02 formulation showed a modified release profile compared to pure AMTAC 02. The <i>in vivo</i> assay demonstrated that the system has a tumor inhibition potential 6 times greater than the untreated group. The data suggested that NLC-AMTAC 02-mediated SDT could represent a promising treatment modality for BC.