[Frontiers in Bioscience S4, 988-1006 , January 1, 2012]

Advances in sonoporation strategies for cancer

Olga Zolochevska1, Marxa L. Figueiredo1

1 Department of Pharmacology and Toxicology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX 77555

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Advances in molecular therapy using sonoporation
3.1. Delivery of small molecules by sonoporation
4. Advances in sonoporation for cancer gene therapy
4.1. Delivery of pDNA
4.1.1. Immunogene pDNA sonotherapy
4.1.2. Cytotoxic and proapoptotic sonotherapy
4.1.3. Optimizing conditions for pDNA sonoporation in vivo
4.2.Other nucleic acid sonoporation gene therapy
4.2.1. Sonotherapy with pDNA and polymer complexes
4.2.2. siRNA sonotherapy
4.2.3. Enhancing viral gene delivery by sonoporation
5.Sonoporation and future directions
5.1. Targeting of microbubbles
5.2. Improving localized sonotherapy
5.3. Extending sonotherapy to treat the tumor microenvironment: cancer-associated bone lesions
5.4. Microdevices
6. Summary and perspective
7. Acknowledgments
8. References

1. ABSTRACT

We will focus on the therapeutic applications of ultrasound (US) for gene transfection or 'sonoporation'. Sonoporation therapy or 'sonotherapy' is an emerging physical method for delivering drugs and/or nucleic acids for treating cancer. Because of its non-invasive nature, sonotherapy has the potential to be competitive with other treatment delivery methods such as viruses or lipofection. For nucleic acid delivery, sonoporation in the presence of microbubbles (MB) significantly enhances transfection efficiency. Sonoporation is an ideal means of delivering pDNA, and it has a similar efficiency as electroporation or other physical gene therapy techniques, with potentially fewer side effects. Typically, nonphysical means of gene delivery have suffered from lower efficiencies compared to viral vectors, however, several studies suggest that sonoporation pDNA delivery could be a simple and inexpensive method that only requires a plasmid, MB, and a sonoporation device. Sonoporation could also be used to target MB to certain cells/tissues, delivering localized therapies. Using high-performance probes, more precise and safer sonoporation treatments will be developed, and newer therapeutic prospects will be realized.