Suppressing or Enhancing Macrophage Engulfment through the Use of CD47 and Related Peptides

Abstract

Foreign particles and microbes are rapidly cleared by macrophages in vivo, although many key aspects of uptake mechanisms remain unclear. “Self” cells express CD47 which functions as an anti-phagocytic ligand for SIRPα on macrophages, particularly when pro-phagocytic ligands such as antibodies are displayed in parallel. Here, we review CD47 and related “Self” peptides as modulators of macrophage uptake. Nanoparticles conjugated with either CD47 or peptides derived from its SIRPα binding site can suppress phagocytic uptake by macrophages in vitro and in vivo, with similar findings for CD47-displaying viruses. Drugs, dyes, and genes as payloads thus show increased delivery to targeted cells. On the other hand, CD47 expression by cancer cells enables such cells to evade macrophages and immune surveillance. This has motivated development of soluble antagonists to CD47-SIRPα, ranging from blocking antibodies in the clinic to synthetic peptides in preclinical models. CD47 and peptides are thus emerging as dual-use phagocytosis modulators against diseases.

Preparation and PET/CT imaging of implant directed 68Ga-labeled magnetic nanoporous silica nanoparticles

“…It is also discussed whether PEGylation may negatively influence nanoparticles’ performance as drug carriers because it hinders nanoparticle-cell interactions [ 67 ]. To further improve the half-life of nanoparticles in the bloodstream whilst avoiding PEGylation shortcomings some more biologically inspired strategies have been evolved, like coating with cell membranes [ 31 , 32 , 75 , 76 ] or functionalization with CD47 [ 30 , 55 , 77 , 78 ].…”

“…Accordingly, most of the nanoparticles are cleared from the circulation and get stuck in organs belonging to the reticuloendothelial system (RES) like liver and spleen before they can even reach their target [ 27 ]. Due to that fact, researchers focused on which characteristics of nanoparticles can influence this identification by the immune system and developed various strategies to overcome recognition by cells of the MPS like conjugation with polyethylene glycol (PEG) [ 28 , 29 ], CD47 [ 30 ] or cloaking with membranes of blood cells [ 31 , 32 ]. A recent in vivo study used PEGylated, magnetic silica nanoparticles and proved them as biocompatible in mice [ 33 ].…”

A New Serum Macrophage Checkpoint Biomarker for Innate Immunotherapy: Soluble Signal-Regulatory Protein Alpha (sSIRPα)

“…This is supported by the observed increase in sSIRPα after pro-inflammatory activation both in vitro and in vivo. Importantly, the activation may also shift the balance between soluble and cell-bound SIRPα, resulting in a decreased CD47 binding of cellular SIRPα due to blockage by increasing sSIRPα [ 25 , 26 ].…”

TME-Related Biomimetic Strategies Against Cancer

“… 75 Another strategy is to modify CD47 on nanoparticles and bind with signal regulatory proteins (SIRP) on phagocytes to inhibit the phagocytic ability of macrophages, ultimately avoiding the nanoparticles from being engulfed by macrophages. 76 , 77 Biocoupling technology used to modify CD47 on nanoparticles may lead to protein denaturation. 78 Therefore, CD47 simulated peptides can be used instead, but these peptides are different from SIRP α.…”