Engineering cell mechanics for targeted drug delivery
Cell therapy represents the future therapeutic landscape for treating diseases including cancer, infections and autoimmune disorders. While the interplay between mechanics and biology has been widely studied and emphasized in healthy and disease cells, its influence on engineered cells is often overlooked in the development of cell therapy. For example, when cell surface is decorated with drug-encapsulating particles, many open questions remain about how particle parameters influence cell mechanics and drug targeting efficiency. The natural targeting mechanism of blood cells (red blood cells, platelets, T cells, monocytes, natural killer cells etc.) deforming and traveling via microcirculation from the site of injection to the site of action is influenced by particles to an unknown extent, leading to concerns of side effects as well as engineering opportunities for controlling drug biodistribution. Our aim is to develop theoretical models of engineered cell mechanics based on particle-membrane interactions to guide drug carrier design. In recent work, we have shown that cell membrane tension induced by nanoparticle attachment can significantly alter particle uptake by engineered cells. This increased tension can block endocytosis and induce changes in particle adsorption isotherms and shear-induced particle detachment as in blood vessels. This platform technology has significant translational effects because the design of ideal drug carriers involves a large parameter space, and its optimization cannot be efficiently translated from animal models to human.
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