Cellular Surface Engineering via Multilayered Polymer Nanostructures

Technology #12846

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FIG. 1D is an overview of the cell functionalization scheme. Panel (a) shows a regular array of surface-bound patches spaced 50 μm apart. The green fluorescence is from FITC-PAH. Panel (b) shows that after cell incubation and attachment, a majority of the surface-bound patches are occupied. Panel (c) shows that the patches were released from the surface while remaining attached to the cell membrane.FIG. 2 is a schematic diagram of the "lift-off" method of making patches.FIG. 3 is a schematic diagram of the plasma etching method of making patches.FIG. 19 is a time sequence of images depicting a magnetic patch associated with an individual cell.
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Inventors
Professor Robert Cohen
Department of Chemical Engineering, MIT
External Link (cohengroup.mit.edu)
Professor Michael Rubner
Department of Materials Science and Engineering, MIT
External Link (web.mit.edu)
Albert Swiston
Department of Materials Science and Engineering, MIT
Professor Darrell Irvine
Department of Materials Science and Engineering, MIT
External Link (irvine-lab.mit.edu)
Managed By
Jim Freedman
MIT Technology Licensing Officer - Chemicals, Instruments, Consumer Products
Patent Protection

Synthetically Functionalized Living Cells

US Patent 8,323,637

Synthetically Functionalized Living Cells

US Patent Pending 2014-0127774
Publications
Surface Functionalization of Living Cells with Multilayer Patches
Nano Letters, 2008, 8 (12), pp 4446–4453
Freely Suspended Cellular “Backpacks” Lead to Cell Aggregate Self-Assembly
Biomacromolecules, 2010, 11 (7), pp 1826–1832
Cell-Based Drug Delivery Devices Using Phagocytosis-Resistant Backpacks
Advanced Materials, 2011, 23 (12), pp. H105-H109

Applications

This technology for modifying the surface properties of living cells has medical applications in the targeted delivery of drugs or imaging agents. It could also be applied in the biotech industry to create tissue constructs without relying on large extracellular scaffolds. Finally, the unprecedented control this technology provides over cell surface characteristics opens up new areas of basic research in cellular biology and immune system engineering.

Problems Addressed

Existing in vivo methods of modifying the surface composition of living cells such as DNA transfection are restricted to molecules that can be produced by the cell’s natural gene expression machinery. While the incorporation of synthetic materials into live cell membranes have been attempted, these techniques often deposit a uniform coating which occludes the cell surface and interferes with useful cell-environment interactions.

Macrophages are a class of human immune cells which could be modified to deliver drugs or imaging agents to targeted locations in the body. However, they are prone to internalizing foreign particles introduced to their surfaces using traditional approaches, thereby impairing the capability of these approaches to introduce surface modifications.

This technology overcomes these limitations by modifying the surface composition of live cells without interfering with their viability or ability to communicate and interact with the environment.

Technology

This technology enables modification of a cell’s surface properties while preserving most of its native behavior by attaching a polyelectrolyte multilayer (PEM) patch to the cell. A PEM is first assembled on a planar substrate through an aqueous-based layer-by-layer (LbL) process which takes place in the absence of living cells. This allows the use of a wide range of assembly conditions including cytotoxic chemistries. This PEM is then patterned into a number of discontiguous patches using photolithography-based techniques like "lift-off" and plasma etching or polymer-on-polymer stamping (POPS).

The PEM patches used in this technology generally consists of a labile releasable layer dissociable under non-cytotoxic conditions, a functional or payload layer customizable for different applications, and a cytophilic layer with specific affinity for surface ligands of a predetermined cell type. Additional layers may be incorporated to augment substrate adhesion or to improve release properties. Once PEM patch fabrication is complete, target cells are incubated with the substrate-bound patches whereupon they bind to the cytophilic layer of the patch. Finally, relevant environmental conditions, such as pH or the presence of a specific enzyme, are modified to break down the labile layer and release the cell-patch complex from the substrate.

The end result of this process is a viable cell with a functionalized PEM patch covering only part of its surface, leaving the remainder to mediate native cellular interactions.

Advantages

  • Retains native cellular interactions and functionality
  • Compatible with wide range of PEM assembly conditions and materials without regard to cytotoxicity
  • Customizable to carry a wide variety of functional payloads including drugs, proteins, and nanoparticles
  • Deposited patches resist internalization when applied to phagocytic cells