TY - JOUR
T1 - Remotely Guided Immunobots Engaged in Anti-Tumorigenic Phenotypes for Targeted Cancer Immunotherapy
AU - Dogan, Nihal Olcay
AU - Ceylan, Hakan
AU - Suadiye, Eylül
AU - Sheehan, Devin
AU - Aydin, Asli
AU - Yasa, Immihan Ceren
AU - Wild, Anna Maria
AU - Richter, Gunther
AU - Sitti, Metin
N1 - Publisher Copyright:
© 2022 The Authors. Small published by Wiley-VCH GmbH.
PY - 2022/11/17
Y1 - 2022/11/17
N2 - Building medical microrobots from the body's own cells may circumvent the biocompatibility concern and hence presents more potential in clinical applications to improve the possibility of escaping from the host defense mechanism. More importantly, live cells can enable therapeutically relevant functions with significantly higher efficiency than synthetic systems. Here, live immune cell-derived microrobots from macrophages, i.e., immunobots, which can be remotely steered with externally applied magnetic fields and directed toward anti-tumorigenic (M1) phenotypes, are presented. Macrophages engulf the engineered magnetic decoy bacteria, composed of 0.5 µm diameter silica Janus particles with one side coated with anisotropic FePt magnetic nanofilm and the other side coated with bacterial lipopolysaccharide (LPS). This study demonstrates the torque-based surface rolling locomotion of the immunobots along assigned trajectories inside blood plasma, over a layer of endothelial cells, and under physiologically relevant flow rates. The immunobots secrete signature M1 cytokines, IL-12 p40, TNF-α, and IL-6, and M1 cell markers, CD80 and iNOS, via toll-like receptor 4 (TLR4)-mediated stimulation with bacterial LPS. The immunobots exhibit anticancer activity against urinary bladder cancer cells. This study further demonstrates such immunobots from freshly isolated primary bone marrow-derived macrophages since patient-derivable macrophages may have a strong clinical potential for future cell therapies in cancer.
AB - Building medical microrobots from the body's own cells may circumvent the biocompatibility concern and hence presents more potential in clinical applications to improve the possibility of escaping from the host defense mechanism. More importantly, live cells can enable therapeutically relevant functions with significantly higher efficiency than synthetic systems. Here, live immune cell-derived microrobots from macrophages, i.e., immunobots, which can be remotely steered with externally applied magnetic fields and directed toward anti-tumorigenic (M1) phenotypes, are presented. Macrophages engulf the engineered magnetic decoy bacteria, composed of 0.5 µm diameter silica Janus particles with one side coated with anisotropic FePt magnetic nanofilm and the other side coated with bacterial lipopolysaccharide (LPS). This study demonstrates the torque-based surface rolling locomotion of the immunobots along assigned trajectories inside blood plasma, over a layer of endothelial cells, and under physiologically relevant flow rates. The immunobots secrete signature M1 cytokines, IL-12 p40, TNF-α, and IL-6, and M1 cell markers, CD80 and iNOS, via toll-like receptor 4 (TLR4)-mediated stimulation with bacterial LPS. The immunobots exhibit anticancer activity against urinary bladder cancer cells. This study further demonstrates such immunobots from freshly isolated primary bone marrow-derived macrophages since patient-derivable macrophages may have a strong clinical potential for future cell therapies in cancer.
KW - cancer immunotherapy
KW - cell-based microrobots
KW - immune cells
KW - immunomodulation
KW - macrophages
UR - http://www.scopus.com/inward/record.url?scp=85139444755&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85139444755&partnerID=8YFLogxK
U2 - 10.1002/smll.202204016
DO - 10.1002/smll.202204016
M3 - Article
C2 - 36202751
AN - SCOPUS:85139444755
SN - 1613-6810
VL - 18
JO - Small
JF - Small
IS - 46
M1 - 2204016
ER -