Ultrasonic cell therapy via nanocarrier-based nucleus delivery of a molecular sonosensitizer

The therapeutic performance of drugs is often limited by the inefficient targeting/delivery to intracellular targets. This study presents the engineered polymeric nanomicelle-based nuclear delivery of molecular sonosensitizers with enhanced therapeutic performance under ultrasound exposure. A nanocarrier was designed with exposed guanidinium groups that interact with cell membrane phosphates, enabling direct translocation into the cytosol and delivering the molecular sonosensitizer to the nucleus, bypassing endocytosis and lysosomal trapping. The nuclear delivery of sonosensitizers offers apoptotic cell death upon ultrasound exposure by producing reactive oxygen species around the nucleus. Control nanocarrier-based cytosolic delivery of the sonosensitizer showed 4 times lower cytotoxicity under similar conditions. Our findings demonstrate the potential of subcellular targeting/delivery for enhanced therapeutic performance.