Immunoregulation of macrophages by dynamic ligand presentation via ligand-cation coordination

Abstract

Macrophages regulate host responses to implants through their dynamic adhesion, release, and activation. Herein, we employ bisphosphonate (BP)-coated gold nanoparticle template (BNP) to direct the swift and convertible formation of Mg²⁺-functional Mg²⁺-BP nanoparticle (NP) on the BP-AuNP surface via reversible Mg²⁺-BP coordination, thus producing (Mg²⁺-BP)-Au dimer (MgBNP). Ethylenediaminetetraacetic acid-based Mg²⁺ chelation facilitates the dissolution of Mg²⁺-BP NP, thus enabling the reversion of the MgBNP to the BNP. This convertible nanoassembly incorporating cell-adhesive Mg²⁺ moieties directs reversible attachment and detachment of macrophages by BP and EDTA, without physical scraping or trypsin that could damage cells. The swift formation of RGD ligand- and Mg²⁺-bifunctional RGD-Mg²⁺-BP NP that yields (RGD-Mg²⁺-BP)-Au dimer (RGDBNP) further stimulates the adhesion and pro-regenerative M2-type polarization of macrophages, both in vitro and in vivo, including rho-associated protein kinase. This swift and non-toxic dimer formation can include diverse bio-functional moieties to regulate host responses to implants.