Co-coating of receptor-targeted drug nanocarriers with anti-phagocytic moieties enhances specific tissue uptake versus non-specific phagocytic clearance. (December 2017)

• Record Type: Journal Article
• Authors: Kim, Joshua; Sinha, Sauradeep; Solomon, Melani; Perez-Herrero, Edgar; Hsu, Janet; Tsinas, Zois; Muro, Silvia
• Is Part Of: Biomaterials. Volume 147(2017)
• Page Start: 14
• Page End: 25
• Publication Date: 2017-12
• Subjects: Targeted drug nanocarriers -- Receptor-mediated endocytosis -- Phagocytic clearance -- CD47 -- Biodistribution; Amil amiloride -- BSA bovine serum albumin -- CAM cellular adhesion molecule -- Fil filipin -- HUVECS human umbilical vein endothelial cells -- ICAM-1 intercellular adhesion molecule 1 -- ID injected dose -- ID/g injected dose per gram of tissue -- IgG immunoglobulin G -- MDC monodansylcadaverine -- NCs nanocarriers -- PECAM-1 platelet-endothelial cell adhesion molecule 1 -- TNFα tumor necrosis factor alpha -- TfR transferrin receptor -- PLGA poly(D.L-lactide-co-glycolic) acid; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2017.08.045
• Languages: English
• ISSNs: 0142-9612

Abstract

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% for 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 (0.99-fold) to 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. Graphical abstract: Surface functionalization of drug nanocarriers with both CD47 and targeting moieties provides anti-phagocytic properties for reduced non-specific clearance while enabling specific receptor-mediated uptake by target tissue cells. Image 1