Gonzalez, Maria

Diseases of the central nervous system commonly affect motoneurons. In particular, spinal cord injury, aging and neurological disorders can cause motoneuron dysfunction or loss. There are no effective diagnostic tools or treatments that specifically target motoneurons. We hypothesized that nanoparticles can be used to target drug delivery to motoneurons. Specifically, mesoporous silica nanoparticles (MSNPs) may be ideal since they can be independently modified allowing loading of various cargos and surface‐engineered for bio‐functionality. The aim of this study was to characterize the role of nanoparticle size, concentration, time of incubation and surface coating on uptake by cultured motoneurons. Four different fluorescently‐labeled MSNPs were evaluated: PEG‐PEI‐Ace MSNPs of 150 nm and 50 nm, lipid coated MSNPs (protocell ‐ 140 nm) and PEG‐PEI MSNPs (50nm). PEG‐PEI‐Ace showed significant greater motoneuron uptake (p<0.05) after longer periods of incubation (12h for 50 nm & 24h for 150 nm). Protocells and PEG‐PEI achieved maximal uptake by 3h. Differentiated motoneurons displayed significant uptake at cell soma and dendrites. Regardless of cell density and duration of treatment, there was minimal evidence of cytotoxicity by any MSNP. In conclusion, MSNPs can be used to target delivery to motoneurons. Specifically, coating, size and concentration affect motoneuron uptake. Smaller and coated PEG‐PEI‐Ace MSNPs showed substantial uptake by motoneurons. These results may help inform the appropriate characteristics of MSNPs for specific in vivo application.