Transport of Adoptive Cell Transfers With Magnetic Helical Microrobots

Adoptive cell transfers (ACTs) can interact specifically with inflamed tissues, but lack a mechanism for transport through viscous biological barriers such as mucus when administered locally. Further, maintaining cell function is challenging due to the loss of cellular phenotypes in diseased microenvironments. In this work, the use of magnetically controlled helical microrobots is examined to transport macrophages through physiologically representative mucus and maintain functional phenotypes through drug elution for improved cell delivery. Two-photon lithography and sputter coating are used to fabricate helical particles that are embedded with a small molecule drug, dexamethasone, and coated with nickel and titanium. The attachment of macrophages to the helices and the analysis of how the cells influence the trajectories of cell-helix complexes when exposed to a rotating magnetic field are investigated. Additionally, the transport of complexes is compared in aqueous solutions and artificial mucus, noting a nonzero cell-helix complex velocity in the most viscous mucus for potential therapeutic implications. It is found that attached macrophages display no loss of viability after actuation and exhibit directed polarization toward a prescribed anti-inflammatory phenotype due to the sustained release of dexamethasone from the microrobots. This system provides a proof-of-concept for using magnetically controlled ACTs to enhance the treatment of inflammatory diseases.

adoptive cell transfer; cell delivery; drug delivery; macrophage; magnetic helical particles; microrobot.