The accumulation of therapeutic and imaging agents at target sites is critical to their efficacy, and yet remains a significant barrier in the realm of delivery. Instead of relying on passive accumulation, we have exploited macrophages’ inherent tropic abilities to create cell-based platforms that can represent the next generation in vehicles. To avoid exposure of the cell interior and the cargo to one another, and to improve control over loading and release, we use small molecule-based surface modification strategies, taking advantage of bio-compatible conjugations to modify cells with small molecule imaging/sensing and therapeutic agents. We have shown that a variety of chemical functionalizations can be employed and do not affect the properties of macrophages, including their motility and chemotactic responses. The modified cells also continue to localize to and interact with cancer cells, <i>in vitro</i> and <i>in vivo</i>. Toward therapeutic delivery, we have generated chemical linkers that are cleavable under conditions present in the tumor microenvironment, which includes lower pH and enhanced presence of matrix metalloproteinases. We demonstrate that these moieties can be used in conjunction with the cells to result in environment-specific payload release.

Chemically functionalized macrophages as cell-based delivery tools for cancer

2019 Fall National Meeting

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