Abstract C142: Safety of single-walled carbon nanotubes for delivery of siRNA

Abstract

Abstract siRNA is a leading potential new cancer therapy but currently lacks an adequate delivery mechanism. Ensysce has been exploring the use of single-walled carbon nanotubes (SWCNT) as delivery vehicles for siRNA delivery and has previously reported on the in vitro and in vivo efficacy of this platform. This study was conducted to determine what if any toxicities result from the use of SWCNT and identify toxicities that may be directly attributed to this delivery vehicle. For this application, it is not only necessary to determine the maximal load of SWCNT that can be tolerated, the dose limiting toxicities and the fate of the material in the body, but also to carefully prepare the SWCNT suspensions to ensure that contaminating metals, nanotube aggregates and other materials are not present when administered systemically. Ensysce Biosciences has been exploring the safe use of this material and here presents its latest findings from a toxicology study where the total dose of 50 and 100 g of fully suspended and individualized SWCNT were administered to groups of 3 mice. Mice were sacrificed at 12, 24, 48 hr and 1 week following i.v. administration. Blood chemistry and hematology were evaluated at each time point. Urine and feces were collected at 12, and 24 hr. Organs, including spleen, liver, kidney, heart, lung and brain were examined macroscopically and by near IR-fluorescence for the presence of SWCNT. The presence and persistence of SWCNT in the tissues was measured. Data to be presented will include details of the analytical characterization of the SWCNT preparations that were delivered, showing that the tubes were well dispersed and individualized. At both the 24 hr and 1 week timepoints, blood chemistry and hematology showed no evidence of toxicity, as values for all were within the normal ranges. Macroscopic examination of organs indicated that SWCNT were present in liver and spleen at 24 hr. Near IR-fluorescence spectroscopy demonstrated that the nanotube accumulation in the spleen decreased over a 1 week period. Data will be presented showing that a 100 g dose (equivalent to 30 mg in humans) was well tolerated and non-toxic. These studies have led to further work examining limits for use of SWCNT for siRNA delivery, including stability of the siRNA complexes in serum, siRNA loading efficiency and systemic efficacy. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):C142.