Saujanya Laxmirajam Gosangari PhD, Abstract Co-Author: Nothing to Disclose

Kenneth Lloyd Watkin, Presenter: Nothing to Disclose

Lysyl oxidase is highly expressed by metastatic cell lines and has an important role to play in enhancing the process of metastasis. The purpose of in vitro this study was to determine if ultrasound mediated delivery of nanoparticles containing siRNA in their aqueous core can sufficiently suppress the expression of LOX gene, thereby inhibiting metastasis of highly invasive cancer cell lines.

Highly metastatic (MDA-MB-231, Hs578t) and poorly metastatic (MCF-7) cell lines were maintained in RPMI 1640 with serum extender. Upon reaching adequate confluence the cells were seeded in Matrigel Invasion Chamber systems (BD Biosciences). The cells were divided into various treatment groups, control, free siRNA, encapsulated siRNA, free siRNA with ultrasound, and encapsulated siRNA with ultrasound. The power delivered was 0.01 W/cm2 at 7.5 MHz.

No significant difference in percent invasion was found for the poorly metastatic cell line. For the highly metastatic cell lines, the passive release condition did not result in significant suppression of percent invasion. For the active release using ultrasound there was a 6% (MDA-MB-231) and 7% (Hs578t) statistically significant (p<0.004); (p<0.007) decrease in percent invasion respectively when compared to the passive release condition. Ultrasound mediated delivery of siRNA resulted in a significant decrease in percent invasion when compared to raw siRNA (p<0.01). There was no significant difference in percent invasion with raw siRNA compared to siRNA treated with ultrasound.

From the above results it is evident that the metastasis of cell lines was inhibited significantly using ultrasound mediated delivery of the encapsulated siRNA from the nanoparticles. This method of delivery has the potential to help achieve high local release and low systemic toxicity.

The delivery mechanism proposed above can encapsulate and site-specifically deliver therapeutic amounts; hence it is beneficial for inhibiting metastasis which is a key issue in cancer management.

Gosangari, S, Watkin, K, Ultrasound Mediated Delivery of siRNA Nanoparticles Inhibits Metastatic Cancer.  Radiological Society of North America 2006 Scientific Assembly and Annual Meeting, November 26 - December 1, 2006 ,Chicago IL. http://archive.rsna.org/2006/4430539.html