Abstract 5684: Sustained Gene Silencing by Liposomal Sirna Incorporated Mesoporous Silicon Particles

Abstract The use of small interfering RNA (siRNA) technology has rapidly become an attractive revolutionary tool in silencing gene expression and holds potential as a therapeutic strategy in cancer and other diseases. However, for siRNA-based therapeutics to become a reality, an efficient method for in vivo systemic delivery is needed. Here, we demonstrate effective and sustained delivery of siRNA using mesoporous silicon particles (MSP). We first developed a novel variant of multistage MSP by tuning the size and shape properties, which can load dioleoyl phosphatidylcholine (DOPC) nanoliposomes containing siRNA. To test this concept, we targeted EphA2 oncoprotein, which is highly overexpressed in most cancers such as breast, lung, pancreas and ovarian carcinoma. MSP incorporated with EphA2 siRNA-DOPC (MSP-siEphA2-DOPC) resulted in effective gene silencing for up to 15 days after single i.v. injection into mice bearing either SKOV3ip1 or HeyA8.MDR ovarian tumors in the peritoneal cavity. In addition, with a single injection of MSP-siEphA2-DOPC given every 15 days during 6 weeks of treatment, there was significant reduction (83%, P** 0.0032, 64%, P* 0.028, 36%, P, ns 0.0032) of tumor weight and number of nodules in a dose dependent manner (15,10 and 5 µg/mice) respectively compared with control groups. Furthermore, when we administrated MSP-siEphA2-DOPC in combination with either paclitaxel or docetaxel, we observed 87% and 91% tumor reduction compared to the control group respectively. Taken together, MSP-siEphA2-DOPC provides a new approach for sustained release of siRNA into disease sites without repetition of injection. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5684. doi:1538-7445.AM2012-5684