Ultrasonic Cell Therapy via Nanocarrier-Based Nucleus Delivery of Molecular Sonosensitizer

Abstract

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