Abstract
Macrophages are key immune cells that perform various physiological functions, such as the maintenance of homeostasis, host defense, disease progression, and tissue regeneration. Macrophages adopt distinctly polarized phenotypes, such as pro-inflammatory M1 phenotype or anti-inflammatory (pro-healing) M2 phenotype, to execute disparate functions. The remotely controlled reversible uncaging of bioactive ligands, such as Arg-Gly-Asp (RGD) peptide, is an appealing approach for temporally regulating the adhesion and resultant polarization of macrophages on implants in vivo. Here, we utilize physical and reversible uncaging of RGD by a magnetic field that allows facile tissue penetration. We first conjugated a RGD-bearing gold nanoparticle (GNP) to the substrate and then a magnetic nanocage (MNC) to the GNP via a flexible linker to form the heterodimeric nanostructure. We magnetically manipulated nanoscale displacement of MNC and thus its proximity to the GNP to reversibly uncage and cage RGD. The uncaging of RGD temporally promoted the adhesion and subsequent M2 polarization of macrophages while inhibiting their M1 polarization both in vitro and in vivo. The RGD uncaging-mediated adhesion and M2 polarization of macrophages involved rho-associated protein kinase signaling. This study demonstrates physical and reversible uncaging of RGD to regulate the adhesion and polarization of host macrophages in vivo. This approach of magnetically regulating the heterodimer conformation for physical and reversible uncaging of RGD offers the promising potential to manipulate inflammatory or tissue-regenerative immune responses to the implants in vivo.
Original language | English (US) |
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Pages (from-to) | 5978-5994 |
Number of pages | 17 |
Journal | ACS nano |
Volume | 12 |
Issue number | 6 |
DOIs | |
State | Published - Jun 26 2018 |
Funding
Project 31570979 is supported by the National Natural Science Foundation of China. This work is supported by a General Research Fund grant from the Research Grants Council of Hong Kong (Project Nos. 14202215 and 14220716); the Health and Medical Research Fund, the Food and Health Bureau, the Government of the Hong Kong Special Administrative Region (Reference Nos. 04152836 and 03140056); the project BME-p3-15 of the Shun Hing Institute of Advanced Engineering, The Chinese University of Hong Kong; the Chow Yuk Ho Technology Centre for Innovative Medicine, The Chinese University of Hong Kong. The work was partially supported by grants from Research Grants Council of the Hong Kong Special Administrative Region, China (Project Nos. 14119115, 14160917, 9054014 N_CityU102/15, and T13-402/17-N); National Natural Science Foundation of China (81772404, 81430049, and 81772322); Hong Kong Innovation Technology Commission Funds (ITS/UIM-305). This study was also supported in part by SMART program, Lui Che Woo Institute of Innovative Medicine. This work made use of the EPIC facility of Northwestern University’s NUANCE Center, which has received support from the Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource (NSF ECCS-1542205); the MRSEC program (NSF DMR-1720139) at the Materials Research Center; the International Institute for Nanotechnology (IIN); the Keck Foundation; and the State of Illinois, through the IIN.
Keywords
- heterodimer
- macrophage adhesion
- macrophage polarization
- magnetic nanocaging
- remote manipulation
- reversible caging
ASJC Scopus subject areas
- General Materials Science
- General Engineering
- General Physics and Astronomy