Brain-penetrating Particles

In all tissues, including the brain, there is a dense matrix of structural proteins referred to as the extracellular space (ECS). In order to spread throughout tissue, any medicine or nanomedicine must penetrate through the ECS and reach individual target cells. It was previously thought that only very small nanoparticles would be able to penetrate the brain ECS, limiting the therapeutic potential of nanotechnology-based platforms in the brain. At the Center for Nanomedicine (CNM) at Wilmer, we discovered that if nanoparticles are coated in a certain way, they can be twice as large as the previous estimate, and will penetrate much farther into the tissue. We are further evaluating the benefits of brain-penetrating nanoparticles (BPN), including improved tumor tissue penetration and efficacy in glioma models (see “CNS” under Research). Additionally, we anticipate that BPN will also have improved tissue penetration properties in many other types of normal and tumor tissues.

Selected Publications

• Mead BP, Mastorakos P, Suk JS, Klibanov AL, Hanes J, Price RJ. (2015) Targeted gene transfer to the brain via the delivery of brain-penetrating DNA nanoparticles with focused ultrasound, J Control Release, in press.
• Mastorakos P, Zhang C, Berry S, Oh Y, Lee S, Eberhart CG, Woodworth GF, Suk JS, Hanes J. (2015) Highly PEGylated DNA nanoparticles provide uniform and widespread gene transfer in the brain. Adv Healthc Mater, 4(7):1023-33.
• EA Nance, GF Woodworth, KA Sailor, T-Y Shih, Q Xu, G Swaminathan, D Xiang, C Eberhardt, and J Hanes (2012). A dense polyethylene glycol coating improves penetration of large polymeric nanoparticles within brain tissue. Science Translational Medicine, 4(149), p. 149ra119.