(147a) Delivering Cellular Backpacks to Lungs Via Hitchhiking on Monocytes

Targeted delivery of drugs and imaging agents to inflamed tissues, as in the cases of cancer, Alzheimer’s, Parkinson’s disease, and arthritis, represents one of the major challenges facing nanomedicine. Recent studies have utilized the unique abilities of circulatory mammalian cells to control the in vivo fate of polymeric drug carriers. Monocytes, in particular, routinely target and penetrate deep into sites of inflammation, unlike all clinically approved nanomedicines. Here, we describe an approach to take advantage of the natural ability of monocytes to target inflammation by attaching a flat polymeric particle, dubbed a “Cellular Backpack”, that attaches strongly to monocytes through specific antibody interactions. We show that monocytes with backpacks attached retain two important cellular functions, transmigration through endothelial layers and differentiation into macrophages, which are essential for targeting the backpack to desirable tissues. Backpack-laden monocytes exhibit ~2-fold increase in in vivo targeting to lungs following induced local lung inflammation. The backpack’s ability to attach to monocytes, without loss of essential monocyte functions, and ‘hitchhike’ to inflamed tissues offer a new platform for both cell-mediated therapies and targeting to inflamed tissues.