Functionalized Meso-porous Silica Nanoparticles: Biocompatibility and Biodistribution

The focus for gene therapy treatment of disease in recent years has shifted towards the development of non-viral carrier systems because of their biocompatibility and low immunogenicity. We have recently identified novel ‘protocells’ consisting of amorphous mesoporous silica nanoparticles that support lipid bilayers as promising gene and drug delivery carriers to brain and spinal cord following peri-spinal delivery into the subarachnoid space (intrathecal; i.t.). Specifically, positively charged, 1, 2-Dioleoyl-3-Trimethylammonium-Propane (DOTAP) -cholesterol (DOTAP:Chol) liposome-formulated protocells revealed optimal in vitro cargo release kinetics and cellular IL-10 transgene transfection in cell cultures. However, little work has been conducted on treatment possibilities for neurological diseases such as chronic neuropathic pain. In the present work, we examined the biodistribution using small animal Single Photon Emission Computed Tomography (SPECT) following Iodinated (I¹²⁵)-protocells injected by i.t. or intravenous (i.v.) route. Following i.v. and i.t.  I¹²⁵-protocells in separate groups of rats (N=2), SPECT imaging (dorsal, ventral, and cross-sections) was evaluated at 0,5,24 and at weekly intervals for 8 weeks, or until  I¹²⁵-protocells were no longer detected. SPECT imaging is ongoing, however, i.v. I¹²⁵-protocells rapidly localize to the lungs and redistribute to the filter organs. Conversely, i.t. I¹²⁵-protocells remain highly localized with little diffusion. Additionally, the biocompatibility of I¹²⁵-protocells, or their constituents, will be examined in-vitro in murine macrophage cells (RAW 264.7). Pilot data indicate that cells lacked  elevated nitric oxide, a pro-infalmmatory molecule released during inflammation. Protocell vectors offer amenable biological characteristics for therapeutic gene transfer.