Crossing the Blood Brain Barrier: a Potential Application of Myristoylated Polyarginine for in vivo Neuroimaging

As basic neurological research continues to reveal novel targets for therapy the necessity to deliver therapeutic agents across the blood brain barrier (BBB) becomes of the paramount importance. If developed, delivery modules would bring targeting molecules across BBB to their respective active sites. In addition, it would be highly advantageous if bioavailability of these delivered molecules can be monitored over time using non-invasive imaging techniques.

We developed a versatile delivery molecule (MPAP-Cy5.5) based on a myristylated polyarginine capable of crossing the blood brain barrier and accumulating in the brain after intravenous injection. The delivery module consisted of a short amphiphilic myristoylated-polyarginine peptide (MPAP), modified with near-infrared fluorescence dye so that its accumulation and distribution can be monitored over time by in vivo near-infrared optical imaging.

In vivo imaging:

Animals- 5-6wk old nu/nu mice.
Intravenous injection of MPAP-Cy5.5 (2.5 nmol/mouse).
NIRF imaging- 15 min, 30 min, 1 h, 2 h, 3 h, 6 h, 24 h, and 44 h after injection of the probe.
Correlative fluorescence microscopy on frozen brain sections.

We report for the first time the distribution of the delivery module in vivo over time to the brain of a mouse using near-infrared fluorescence (NIRF) imaging.