Co-coating of receptor-targeted drug nanocarriers with anti-phagocytic moieties enhances specific tissue uptake versus non-specific phagocytic clearance

Abstract

Nanocarriers (NCs) help improve the performance of therapeutics, but their removal by phagocytes in the liver, spleen, tissues, etc. diminishes this potential. Although NC functionalization with polyethylene glycol (PEG) lowers interaction with phagocytes, it also reduces interactions with tissue cells. Coating NCs with CD47, a protein expressed by body cells to avoid phagocytic removal, offers an alternative. Previous studies showed that coating CD47 on non-targeted NCs reduces phagocytosis, but whether this alters binding and endocytosis of actively-targeted NCs remains unknown. To evaluate this, we used polymer NCs targeted to ICAM-1, a receptor overexpressed in many diseases. Co-coating of CD47 on anti-ICAM NCs reduced macrophage phagocytosis by ~50% up to 24 h, while increasing endothelial-cell targeting by ~87% over control anti-ICAM/IgG NCs. Anti-ICAM/CD47 NCs were endocytosed via the CAM-mediated pathway with efficiency similar to (0.99-fold) anti-ICAM/IgG NCs. Comparable outcomes were observed for NCs targeted to PECAM-1 or transferrin receptor, suggesting broad applicability. When injected in mice, anti-ICAM/CD47 NCs reduced liver and spleen uptake by ~30–50% and increased lung targeting by ~2-fold (~10-fold over IgG NCs). Therefore, co-coating NCs with CD47 and targeting moieties reduces macrophage phagocytosis and improves targeted uptake. This strategy may significantly improve the efficacy of targeted drug NCs.

The Protein Corona as a Confounding Variable of Nanoparticle-Mediated Targeted Vaccine Delivery

“…Rodriguez et al ( 115 ) demonstrated that CD47-derived peptides coupled to polystyrene beads reduced their uptake by macrophages, and prolonged their circulation in mice. In line, different types of NC (polystyrene, PLGA) conjugated with an ICAM-1 targeting antibody for endocytic uptake by activated endothelial cells showed clearly reduced unspecific liver accumulation when conjugated in addition with CD47 ( 116 ). In a different approach, NC were coated with cell membranes derived from red blood cells to exploit their endogenous high level surface expression of CD47 and other “don’t eat me signals” [reviewed in Ref.…”

Biodistribution, biocompatibility and targeted accumulation of magnetic nanoporous silica nanoparticles as drug carrier in orthopedics

“…Therefore, apart from PEG, additional functionalization or coatings are necessary, e.g. binding of CD47 to the surface of the nanoparticles [76,117,118]. Another focus is the enhancement of magnetic properties by equipping nanoparticle cores with higher iron content [43] and design larger implants out of a highly permeable, remanent ferromagnetic material [26], probably with additional surface coatings [52].…”

Alterations in Cellular Processes Involving Vesicular Trafficking and Implications in Drug Delivery

“…The use poly(ethylene glycol) (PEG) to minimize these non-specific interactions, which unfortunately has a similar effect on specific ones, has been extensively discussed [192]. Finally, surface coating of the “don’t eat me” signal provided by cluster of differentiation (CD) 47 on drug carriers has been shown to lower phagocytic internalization [193] without affecting specific binding and uptake by co-coated targeting moieties [194].…”