title: Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes.
abstract: Nanomedicine is a burgeoning industry but an understanding of the interaction of nanomaterials with the immune system is critical for clinical translation. Macrophages play a fundamental role in the immune system by engulfing foreign particulates such as nanoparticles. When activated, macrophages form distinct phenotypic populations with unique immune functions, however the mechanism by which these polarized macrophages react to nanoparticles is unclear. Furthermore, strategies to selectively evade activated macrophage subpopulations are lacking. Here we demonstrate that stimulated macrophages possess higher phagocytic activities and that classically activated (M1) macrophages exhibit greater phagocytic capacity than alternatively activated (M2) macrophages. We show that modification of nanoparticles with polyethylene-glycol results in decreased clearance by all macrophage phenotypes, but importantly, coating nanoparticles with CD47 preferentially lowers phagocytic activity by the M1 phenotype. These results suggest that bio-inspired nanoparticle surface design may enable evasion of specific components of the immune system and provide a rational approach for developing immune tolerant nanomedicines.
authors.affiliation: Department of Neurosurgery, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Qie
authors.affiliation: Department of Neurosurgery, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.|Department of Orthopedics, Zhongshan Hospital, Fudan University, 111 Yixueyuan Road, Xuhui, Shanghai, China.
authors.forename: Hengfeng
authors.initials: H
authors.lastname: Yuan
authors.affiliation: Department of Neurosurgery, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.|Mayo Graduate School, Mayo Clinic College of Medicine, 200 1st Street SW, Rochester, MN, 55902, USA.
authors.forename: Christina A
authors.initials: CA
authors.lastname: von Roemeling
authors.affiliation: Department of Neurosurgery, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.
authors.forename: Yuanxin
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.
authors.forename: Xiujie
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Shih
authors.affiliation: Department of Neurosurgery, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Knight
authors.affiliation: Department of Hematology/Oncology, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.|Department of Cancer Biology, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.
authors.forename: Han W
authors.initials: HW
authors.lastname: Tun
authors.affiliation: Department of Neurosurgery, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Wharen
authors.affiliation: Department of Hematology/Oncology, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.
authors.forename: Wen
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.|Department of Cancer Biology, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.|Department of Neuroscience, Mayo Clinic College of Medicine, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville FL, 32224, USA.
authors.forename: Betty Y S
authors.initials: BY
authors.lastname: Kim
mesh_terms: D000818:Animals; D051928:CD47 Antigen / Q000737:chemistry; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology / Q000502:physiology*; D008810:Mice, Inbred C57BL; D053758:Nanoparticles / Q000737:chemistry*; D010587:Phagocytosis; D010641:Phenotype; D011092:Polyethylene Glycols / Q000737:chemistry; D011137:Polystyrenes
chemical_list: D051928:CD47 Antigen; D011137:Polystyrenes; D011092:Polyethylene Glycols