Niklas Choteschovsky
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Research Subjects
Research Interests
Niklas Choteschovsky has a total of 6 co-authors. Here are the top co-authors by number of shared publications:
- Adrian Klefenz
Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany
1 shared publication - Detlef Schuppan
Institute for Translational Immunology and Research Center for Immune Therapy, University Medical Center Mainz, 55131 Mainz, Germany
1 shared publication - Leonard Kaps
Department of Dermatology University Medical Center Mainz Germany
1 shared publication - Lutz Nuhn
Institute of Functional Materials and Biofabrication Center of Polymers for Life Universität Würzburg Würzburg Germany
1 shared publication - Nadine Leber
Department of Chemistry, Johannes Gutenberg-University of Mainz, Duesbergweg 10-14, 55128 Mainz, Germany
1 shared publication - Rudolf Zentel
Department of Chemistry, Johannes Gutenberg University Mainz, Duesbergweg 10-14, 55128 Mainz, Germany
1 shared publication
Latest Publications
- Open Access
In Vivo siRNA Delivery to Immunosuppressive Liver Macrophages by α-Mannosyl-Functionalized Cationic Nanohydrogel Particles
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–ManNP were highly colocalized with CD206+ M2-type macrophages on a cellular level, while untargeted NP (NonNP) showed little colocalization and were non-specifically taken up by other liver cells. ManNP did not induce hepatic inflammation or kidney dysfunction, as demonstrated by serological analysis. In conclusion, α-mannosyl-functionalized ManNP direct NP towards M2-type macrophages in diseased livers and prevent unspecific uptake in non-target cells. ManNP are promising vehicles for siRNA and other drugs for immunomodulatory treatment of liver fibrosis and liver cancer.
Open AccessIn Vivo siRNA Delivery to Immunosuppressive Liver Macrophages by α-Mannosyl-Functionalized Cationic Nanohydrogel Particles
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–ManNP were highly colocalized with CD206+ M2-type macrophages on a cellular level, while untargeted NP (NonNP) showed little colocalization and were non-specifically taken up by other liver cells. ManNP did not induce hepatic inflammation or kidney dysfunction, as demonstrated by serological analysis. In conclusion, α-mannosyl-functionalized ManNP direct NP towards M2-type macrophages in diseased livers and prevent unspecific uptake in non-target cells. ManNP are promising vehicles for siRNA and other drugs for immunomodulatory treatment of liver fibrosis and liver cancer.