POLY Kristi Kiick, Gregory Tew, Jeffrey Linhardt  Monday, August 23, 2010 

135 - Injectable cellular “Backpacks” lead to cell aggregate self-assembly

Albert Swiston, Jonathan Gilbert, Darrell Irvine, Robert Cohen, Michael Rubner Department of Materials Science and Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA, United States; Howard Hughes Medical Institute, Chevy Chase, MD, United States

We have demonstrated that multi-functional “backpacks” built from polyelectrolyte multilayers (PEM) films can be attached to living immune system cells. Fabricated using standard photolithographic techniques, backpacks of varying size are built on a glass surface and consists of 3 distinct regions. The first is a releasable region comprised of a poly(methacrylic acid)/poly(vinylpyrrolidone) hydrogen-bonded multilayer that will dissolve above pH 6.4 and release the backpack from the substrate. The next region is the payload and consists of a PLGA/hydrophobic dye strata and Fe3O4 nanoparticle/poly(allylamine hydrochloride) layer. This renders the backpacks magnetic, fluorescent, and partially hydrolysable at physiological conditions. Last, a cell-adhesive outer face is chosen to anchor the backpack to the membrane. We used hyaluronic acid (HA)-containing PEMs to anchor backpacks to B-lymphocytes, since HA is the ligand for CD44, a surface receptor found on these cells. When backpacks are released from the surface and injected into a cell solution, cells will form aggregates as they attach to one or more backpacks. The size of these aggregates is determined both by the size of the backpack and the ratio of backpacks to cells. We show that these aggregates can be forced through small pores (to mimic extravasation), which dissociates the aggregates but does not remove the backpacks from the surfaces of cells. Flow cytometry and laser diffraction of cell-backpack suspensions show that large aggregates can be reversibly de-aggregated, yielding small (ie, less than 3 cells) clusters. Since backpacks do not completely occlude the cellular surface from the environment, this technique allows payloads to be attached to a cell that is still free to perform its native functions requiring intimate environmental interaction. We will discuss how this approach contributes to the new field of bio-hybrid materials and has potential applications in bioimaging, single-cell functionalization, immune system and tissue engineering, and cell-based therapeutics.

Monday, August 23, 2010 10:20 AM
Polymers for Immunology and Immunotherapy (08:30 AM - 11:20 AM)
Location: The Westin Boston Waterfront
Room: Grand Ballroom D


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