TY - JOUR
T1 - Remote Manipulation of Ligand Nano-Oscillations Regulates Adhesion and Polarization of Macrophages in Vivo
AU - Kang, Heemin
AU - Kim, Sungkyu
AU - Wong, Dexter Siu Hong
AU - Jung, Hee Joon
AU - Lin, Sien
AU - Zou, Kaijie
AU - Li, Rui
AU - Li, Gang
AU - Dravid, Vinayak P.
AU - Bian, Liming
N1 - Funding Information:
Project 31570979 is supported by the National Natural Science Foundation of China. The work described in this paper is supported by a General Research Fund grant from the Research Grants Council of Hong Kong (project no. 14202215, 14220716). This work is supported by the Health and Medical Research Fund, the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region (reference no.: 02133356, 03140056). This research was also supported by the project BME-p3-15 of the Shun Hing Institute of Advanced Engineering, The Chinese University of Hong Kong. This research is supported by the Chow Yuk Ho Technology Centre for Innovative Medicine (The Chinese University of Hong Kong). This work was performed at the EPIC facility of Northwestern University’s NUANCE Center with the support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN. We gratefully thank Mr. Gang Yang for the assistance in the experiments.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/10/11
Y1 - 2017/10/11
N2 - Macrophages play crucial roles in various immune-related responses, such as host defense, wound healing, disease progression, and tissue regeneration. Macrophages perform distinct and dynamic functions in vivo, depending on their polarization states, such as the pro-inflammatory M1 phenotype and pro-healing M2 phenotype. Remote manipulation of the adhesion of host macrophages to the implants and their subsequent polarization in vivo can be an attractive strategy to control macrophage polarization-specific functions but has rarely been achieved. In this study, we grafted RGD ligand-bearing superparamagnetic iron oxide nanoparticles (SPIONs) to a planar matrix via a long flexible linker. We characterized the nanoscale motion of the RGD-bearing SPIONs grafted to the matrix, in real time by in situ magnetic scanning transmission electron microscopy (STEM) and in situ atomic force microscopy. The magnetic field was applied at various oscillation frequencies to manipulate the frequency-dependent ligand nano-oscillation speeds of the RGD-bearing SPIONs. We demonstrate that a low oscillation frequency of the magnetic field stimulated the adhesion and M2 polarization of macrophages, whereas a high oscillation frequency suppressed the adhesion of macrophages but promoted their M1 polarization, both in vitro and in vivo. Macrophage adhesion was also temporally regulated by switching between the low and high frequencies of the oscillating magnetic field. To the best of our knowledge, this is the first demonstration of the remote manipulation of the adhesion and polarization phenotype of macrophages, both in vitro and in vivo. Our system offers the promising potential to manipulate host immune responses to implanted biomaterials, including inflammation or tissue reparative processes, by regulating macrophage adhesion and polarization.
AB - Macrophages play crucial roles in various immune-related responses, such as host defense, wound healing, disease progression, and tissue regeneration. Macrophages perform distinct and dynamic functions in vivo, depending on their polarization states, such as the pro-inflammatory M1 phenotype and pro-healing M2 phenotype. Remote manipulation of the adhesion of host macrophages to the implants and their subsequent polarization in vivo can be an attractive strategy to control macrophage polarization-specific functions but has rarely been achieved. In this study, we grafted RGD ligand-bearing superparamagnetic iron oxide nanoparticles (SPIONs) to a planar matrix via a long flexible linker. We characterized the nanoscale motion of the RGD-bearing SPIONs grafted to the matrix, in real time by in situ magnetic scanning transmission electron microscopy (STEM) and in situ atomic force microscopy. The magnetic field was applied at various oscillation frequencies to manipulate the frequency-dependent ligand nano-oscillation speeds of the RGD-bearing SPIONs. We demonstrate that a low oscillation frequency of the magnetic field stimulated the adhesion and M2 polarization of macrophages, whereas a high oscillation frequency suppressed the adhesion of macrophages but promoted their M1 polarization, both in vitro and in vivo. Macrophage adhesion was also temporally regulated by switching between the low and high frequencies of the oscillating magnetic field. To the best of our knowledge, this is the first demonstration of the remote manipulation of the adhesion and polarization phenotype of macrophages, both in vitro and in vivo. Our system offers the promising potential to manipulate host immune responses to implanted biomaterials, including inflammation or tissue reparative processes, by regulating macrophage adhesion and polarization.
KW - Ligand nano-oscillations
KW - SPION
KW - macrophage adhesion
KW - macrophage polarization
KW - remote manipulation
UR - http://www.scopus.com/inward/record.url?scp=85031284442&partnerID=8YFLogxK
U2 - 10.1021/acs.nanolett.7b03405
DO - 10.1021/acs.nanolett.7b03405
M3 - Article
C2 - 28875707
AN - SCOPUS:85031284442
SN - 1530-6984
VL - 17
SP - 6415
EP - 6427
JO - Nano Letters
JF - Nano Letters
IS - 10
ER -