(171d) Cell-Mediated Drug Delivery With Phagocytosis Resistant Polymeric Backpacks

Advances in drug delivery have been enabled by modifying the surface chemistry and, more recently, the shape of particles to target delivery of therapeutics to diseased sites. Recent studies have utilized the unique ability of certain mammalian cells to target and home to sites of inflammation, or disease, by conjugating drug carrying particles directly to the surface of these cells for targeted delivery to these diseased sites(1).  The synergism between particle and cell has great potential to increase the efficiency of drug delivery in the future.

In this work we have developed a polymeric particle termed a backpack that conjugates strongly to monocytes through specific antibody interactions and has many applications in cell-mediated delivery. The backpacks are anisotropic, stratified polymeric thin films that are hundreds of nanometers thick and microns wide. We will discuss the fabrication and applications of backpacks in monocyte-mediated drug delivery. Since the backpack leaves most of the cell surface unaltered, we show that the biological functions and characteristics of monocytes are not changed upon its conjugation with the cell surface. For example, an in vitro transwell assay was used to show that backpack-laden monocytes still perform native functions such as extravasation through an endothelial cell layer in response to a biological stimulus. Furthermore, prior results show that the backpack, due to its unique shape, is resistant to phagocytosis by macrophages(2). The capability to resist internalization while strongly attach to the surface of immune cells such as monocytes and macrophages, uniquely position the backpack for cell-mediated extracellular therapeutic delivery in areas such as arthrosclerosis or cancer.

References:

1.         Stephan MT, Moon JJ, Um SH, Bershteyn A, Irvine DJ (2010) Therapeutic cell engineering with surface-conjugated synthetic nanoparticles. Nat Med16(9):1035-U1135.

2.         Doshi N, et al. (2011) Cell-based drug delivery devices using phagocytosis- resistant backpacks. Adv Mater 23(12):H105-H109.