0000000000282947

AUTHOR

Judith Stickdorn

showing 3 related works from this author

Squaric Ester-Based, pH-Degradable Nanogels: Modular Nanocarriers for Safe, Systemic Administration of Toll-like Receptor 7/8 Agonistic Immune Modula…

2021

Small-molecular Toll-like receptor 7/8 (TLR7/8) agonists hold promise as immune modulators for a variety of immune therapeutic purposes including cancer therapy or vaccination. However, due to their rapid systemic distribution causing difficult-to-control inflammatory off-target effects, their application is still problematic, in particular systemically. To address this problem, we designed and robustly fabricated pH-responsive nanogels serving as versatile immunodrug nanocarriers for safe delivery of TLR7/8-stimulating imidazoquinolines after intravenous administration. To this aim, a primary amine-reactive methacrylamide monomer bearing a pendant squaric ester amide is introduced, which i…

Polymersmedicine.medical_treatmentNanogelsVACCINEPharmacology010402 general chemistry01 natural sciencesBiochemistryMicelleCatalysisArticlePolymerizationchemistry.chemical_compoundColloid and Surface ChemistryAdjuvants ImmunologicSDG 3 - Good Health and Well-beingmedicineMedicine and Health SciencesAnimalsHumansReversible addition−fragmentation chain-transfer polymerizationMicellesTLR8AMIDESDrug CarriersMice Inbred BALB CChemistryOptical ImagingBiology and Life SciencesEstersGeneral ChemistryTLR7Hydrogen-Ion Concentration0104 chemical sciencesImidazoquinolineDrug LiberationCONJUGATIONToll-Like Receptor 7Toll-Like Receptor 8Systemic administrationImmunotherapyNanocarriersADJUVANTSAdjuvantNanogel
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Targeted Repolarization of Tumor‐Associated Macrophages via Imidazoquinoline‐Linked Nanobodies

2021

Abstract Tumor‐associated macrophages (TAMs) promote the immune suppressive microenvironment inside tumors and are, therefore, considered as a promising target for the next generation of cancer immunotherapies. To repolarize their phenotype into a tumoricidal state, the Toll‐like receptor 7/8 agonist imidazoquinoline IMDQ is site‐specifically and quantitatively coupled to single chain antibody fragments, so‐called nanobodies, targeting the macrophage mannose receptor (MMR) on TAMs. Intravenous injection of these conjugates result in a tumor‐ and cell‐specific delivery of IMDQ into MMRhigh TAMs, causing a significant decline in tumor growth. This is accompanied by a repolarization of TAMs to…

Lung NeoplasmsGeneral Chemical Engineeringmedicine.medical_treatmentGeneral Physics and AstronomyMedicine (miscellaneous)TLR 7/8 agonist02 engineering and technology01 natural scienceschemistry.chemical_compoundCancer immunotherapyTumor-Associated MacrophagesTumor MicroenvironmentMacrophageM2 macrophagesGeneral Materials ScienceReceptorResearch ArticlesMice KnockoutMembrane GlycoproteinsChemistrytumor associated macrophagesQGeneral EngineeringImidazoles021001 nanoscience & nanotechnologynanobodiesmedicine.anatomical_structureDrug deliveryQuinolines0210 nano-technologyMannose ReceptorResearch ArticleT cellScience010402 general chemistryBiochemistry Genetics and Molecular Biology (miscellaneous)Immune systemmedicineAnimalsrepolarizationcancer immunotherapyCancerSingle-Domain Antibodiesmedicine.disease0104 chemical sciencesImidazoquinolineMice Inbred C57BLDisease Models AnimalToll-Like Receptor 6Toll-Like Receptor 7drug deliveryCancer research
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Transient Multivalent Nanobody Targeting to CD206-Expressing Cells via PH-Degradable Nanogels

2020

To target nanomedicines to specific cells, especially of the immune system, nanobodies can be considered as an attractive tool, as they lack the Fc part as compared to traditional antibodies and, thus, prevent unfavorable Fc-receptor mediated mistargeting. For that purpose, we have site-specifically conjugated CD206/MMR-targeting nanobodies to three types of dye-labeled nanogel derivatives: non-degradable nanogels, acid-degradable nanogels (with ketal crosslinks), and single polymer chains (also obtained after nanogel degradation). All of them can be obtained from the same reactive ester precursor block copolymer. After incubation with na&iuml

0301 basic medicineEndosomeNanogels02 engineering and technologyConjugated systemArticleM2 macrophage03 medical and health sciencesHumansReversible addition−fragmentation chain-transfer polymerizationlcsh:QH301-705.5targetingchemistry.chemical_classificationRAFT polymerizationChinese hamster ovary cellGeneral MedicinePolymerHydrogen-Ion Concentrationmultivalency021001 nanoscience & nanotechnologynanobody030104 developmental biologyTAMchemistryCD206lcsh:Biology (General)nanogelclick chemistryClick chemistryBiophysicsNanocarriers0210 nano-technologyNanogelCells
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