Thin-film backpacks for cell-based therapies across the blood-brain barrier

Presenter: 

Roberta Polak

Authors: 

Roberta Polak, a,c Reginaldo J. Gomes Neto, a,c Matthew J. Haney, b Natalya L. Klyachko, b Yuling Zhao, b Elena V. Batrakova, b Robert E. Cohen, c Michael F. Rubner, a

Author Affiliation: 

a Department of Materials Science and Engineering, MIT b School of Pharmacy, University of North Carolina at Chapel Hill c Chemical Engineering, MIT

Abstract: 

It remains challenging to deliver therapeutics to the brain. Cellular backpacks are a potentially interesting approach because they can act as drug depots that travel with the attached cell, potentially across the blood-brain barrier. Cellular backpacks are 7-10 _m diameter polymer patches of a few hundred nanometers in thickness that can be fabricated by using layer-by-layer (LbL) assembly onto a photopatterned substrate. Since backpacks can be attached to the surface of living cells without being phagocytized, our goal is to explore the use of backpacks for cell-mediated and targeted drug-delivery throughout the body. Cellular backpacks can be engineered to carry many different types of biologic and small molecule drugs. Additionally, by attaching the desired antibodies on the backpacksÕ surfaces, it is possible to adhere them to a wide variety of cells. Recent developments by our group have demonstrated the ability of backpack-monocyte conjugates to migrate and accumulate in inflamed tissue sites (e.g. lungs and skin). In this work, we show that catalase, an antioxidant enzyme, can be successfully loaded into backpacks at meaningful concentrations with retained activity. Attachment of catalase-loaded backpacks to macrophages enables the non-invasive delivery of drugs to sites of inflammation, especially across the blood-brain barrier, which is a significant obstacle to drug treatment by traditional means such as systemic administration.