Sonoporation
Cell membranes often prevent large molecules such as drugs and genes from entering cells and taking effect. The mechanical force of focused ultrasound, via stable cavitation, can modify the permeability of cell membranes and enhance the absorption of these molecules.
This effect, known as sonoporation, can increase the efficacy of drugs and genes in precise areas in the body1.
Stable cavitation can induce moderate and reversible changes at the cellular level, creating pores in cell membranes, allowing a greater volume of compounds to enter the cell1. Additionally, stable cavitation produces acoustic streaming, which increases the flow of fluid in a cell’s environment. This increase in flow may assist in the opening of the pores, and it also directs the therapeutic molecules toward the cells, which enhances cellular uptake2,3.
Enhanced drug delivery via sonoporation could enable treatment of tumors with dense stroma such as pancreatic tumors, and with less systemic toxicity (i.e. less circulating drug required) than with traditional chemotherapy. Focused ultrasound induced sonoporation is also an attractive option for delivery of genetic material when compared to the alternatives, because it can be used in vivo and can greatly increase the specificity of treatments4. Gene therapy can be used to treat a wide range of indications from immunodeficiency disorders to Parkinson’s disease and even certain types of cancer5–7.
[1] Liang H-D, Tang J, Halliwell M. Sonoporation, drug delivery, and gene therapy. Proc. Inst. Mech. Eng. [H]. 2010;224:343–61.
[2] Collis J, Manasseh R, Liovic P, Tho P, Ooi A, Petkovic-Duran K, et al. Cavitation microstreaming and stress fields created by microbubbles. Ultrasonics. 2010;50:273–9.
[3] Wu J, Ross JP, Chiu J-F. Reparable sonoporation generated by microstreaming. J. Acoust. Soc. Am. 2002;111:1460–4.
[4] Greenleaf WJ, Bolander ME, Sarkar G, Goldring MB, Greenleaf JF. Artificial cavitation nuclei significantly enhance acoustically induced cell transfection. Ultrasound Med. Biol. 1998;24:587–95.
[5] Cavazzana-Calvo M, Hacein-Bey S, Basile G de S, Gross F, Yvon E, Nusbaum P, et al. Gene Therapy of Human Severe Combined Immunodeficiency (SCID)-X1 Disease. Science. 2000;288:669–72.
[6] Kaplitt MG, Feigin A, Tang C, Fitzsimons HL, Mattis P, Lawlor PA, et al. Safety and tolerability of gene therapy with an adeno-associated virus (AAV) borne GAD gene for Parkinson’s disease: an open label, phase I trial. The Lancet. 2007;369:2097–105.
[7] St George JA. Gene therapy progress and prospects: adenoviral vectors. Gene Ther. 2003;10:1135–41.