In Vivo siRNA Delivery to Immunosuppressive Liver Macrophages by alpha-Mannosyl-Functionalized Cationic Nanohydrogel Particles

6533b85cfe1ef96bd12bc0fa

RESEARCH PRODUCT

In Vivo siRNA Delivery to Immunosuppressive Liver Macrophages by alpha-Mannosyl-Functionalized Cationic Nanohydrogel Particles

Lutz Nuhn Nadine Leber Leonard Kaps Niklas Choteschovsky Detlef Schuppan Detlef Schuppan Adrian Klefenz Rudolf Zentel

subject

0301 basic medicine Liver Cirrhosis siRNA delivery THP-1 Cells medicine.medical_treatment mannose targeting Mice 0302 clinical medicine Drug Delivery Systems Fibrosis Macrophage M2 macrophages RNA Small Interfering lcsh:QH301-705.5 Tissue homeostasis Mice Inbred BALB C Chemistry Hydrogels General Medicine Hep G2 Cells Liver 030220 oncology & carcinogenesis Female immunotherapy Mannose receptor Mannose Receptor Receptors Cell Surface gene knock-down Article nanohydrogels 03 medical and health sciences Immune system In vivo medicine Immune Tolerance Animals Humans cancer Lectins C-Type Innate immune system Macrophages fibrosis Immunotherapy Macrophage Activation medicine.disease 030104 developmental biology Mannose-Binding Lectins RAW 264.7 Cells lcsh:Biology (General)Cancer research Nanoparticles Mannose

description

Macrophages are the front soldiers of the innate immune system and are vital for immune defense, tumor surveillance, and tissue homeostasis. In chronic diseases, including cancer and liver fibrosis, macrophages can be forced into an immunosuppressive and profibrotic M2 phenotype. M2-type macrophages overexpress the mannose receptor CD206. Targeting these cells via CD206 and macrophage repolarization towards an immune stimulating and antifibrotic M1 phenotype through RNA interference represents an appealing therapeutic approach. We designed nanohydrogel particles equipped with mannose residues on the surface (ManNP) that delivered siRNA more efficiently to M2 polarized macrophages compared to their untargeted counterparts (NonNP) in vitro. The ManNP were then assessed for their in vivo targeting potential in mice with experimental liver fibrosis that is characterized by increased profibrotic (and immunosuppressive) M2-type macrophages. Double-labelled siRNA-loaded ManNP carrying two different near infrared labels for siRNA and ManNP showed good biocompatibility and robust uptake in fibrotic livers as assessed by in vivo near infrared imaging. siRNA&ndash

year	journal	country	edition	language
2020-08-15

10.3390/cells9081905 https://hdl.handle.net/21.11116/0000-0007-03FC-A21.11116/0000-0006-EE0C-2