| Autor: |
Day NB; Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, Colorado 80303, United States., Orear CR; Biomedical Engineering Program, University of Colorado Boulder, Boulder, Colorado 80303, United States., Velazquez-Albino AC; Department of Chemical Engineering, University of Florida, Gainesville, Florida 32611, United States., Good HJ; Department of Chemical Engineering, University of Florida, Gainesville, Florida 32611, United States., Melnyk A; Department of Chemical Engineering, University of Florida, Gainesville, Florida 32611, United States., Rinaldi-Ramos CM; Department of Chemical Engineering, University of Florida, Gainesville, Florida 32611, United States.; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, Florida 32611, United States., Shields Iv CW; Department of Chemical and Biological Engineering, University of Colorado Boulder, Boulder, Colorado 80303, United States.; Biomedical Engineering Program, University of Colorado Boulder, Boulder, Colorado 80303, United States. |
| Abstrakt: |
Adoptive cell transfer (ACT) therapies are growing in popularity due to their ability to interact with diseased tissues in a specific manner. Disc-shaped particles, or "backpacks", that bind to cellular surfaces show promise for augmenting the therapeutic potential of adoptively transferred cells by resisting phagocytosis and locally releasing drugs to maintain cellular activity over time. However, many ACTs suffer from limited tumor infiltration and retention and lack a method for real-time spatial analysis. Therefore, we have designed biodegradable backpacks loaded with superparamagnetic iron oxide nanoparticles (SPIONs) to improve upon current ACT strategies by (i) controlling the localization of cell-backpack complexes using gradient magnetic fields and (ii) enabling magnetic particle imaging (MPI) to track complexes after injection. We show that magnetic backpacks bound to macrophages and loaded with a proinflammatory drug, resiquimod, maintain anticancer phenotypes of carrier macrophages for 5 days and create cytokine "factories" that continuously release IL-12. Furthermore, we establish that forces generated by gradient magnet fields are sufficient to displace cell-backpack complexes in physiological settings. Finally, we demonstrate that MPI can be used to visualize cell-backpack complexes in mouse tumors, enabling a potential strategy to track the biodistribution of ACTs in real time. |
