Targeting of poly(l-lysine) to organs that propagate prions

Abstract

Poly(l-lysine) was recently discovered to inhibit prion propagation. To develop poly(l-lysine) as a potential therapeutic for prion diseases, the understanding of in vivo poly(l-lysine) behavior is pivotal. Therefore, to determine the poly(l-lysine) distribution in mouse spleen and brain, the primary and ultimate target organs for prions, we performed non-invasive longitudinal in vivo imaging and time course on live mice and ex vivo imaging on mouse organs to confirmed poly(l-lysine) was distributed, including the brain and spleen. By studying the in vivo and ex vivo fluorescence images, characteristic patterns of poly(l-lysine) accumulation and elimination depending on different administration routes were also found. Although only a portion of the administered poly(l-lysine) appears to target the brain and spleen, the specific poly(l-lysine) level in these organs was higher than that previously reported. Furthermore, the poly(l-lysine) retention in the brain and spleen was greater than that found in other organs. These results provide valuable information about poly(l-lysine) behavior in vivo, which will be an aid in designing optimal regimens for potential application of poly(l-lysine) in anti-prion therapeutics.