Suicide Gene Delivery System Mediated by Ultrasound-Targeted Microbubble Destruction: A Promising Strategy for Cancer Therapy

Abstract

The treatment of malignant tumors has always been one of the challenges that have plagued researchers and clinicians. The ideal status in cancer treatment is to eliminate tumor cells while avoiding damage to normal tissues. Different approaches have been investigated to achieve such a goal, and suicide gene therapy has emerged as a novel mode of cancer treatment. This approach involves the delivery of genes encoding enzymes that activate non-toxic prodrugs into cytotoxic metabolites that cause the death of transfected cancer cells. Despite promising results obtained both in vitro and in vivo, this innovative approach has long been stalled in the clinic due to the lack of a suitable delivery system to introduce the suicide gene into cancer cells. Ultrasound-targeted microbubble destruction (UTMD) represents a valuable non-viral vector system for site-specific and noninvasive gene therapy. Ultrasound promotes intracellular uptake of therapeutic agents by increasing vascular and cell membrane permeability, especially in the presence of microbubbles. In this scenario, the true potential of suicide genes can be translated into clinically valuable treatments for patients. This review provides background information on suicide gene therapy and UTMD technology, summarizes the current state of knowledge about UTMD-mediated suicide gene delivery in cancer treatment, and presents an outlook on its future development.