id,collection,dc.contributor.author,dc.date.accessioned,dc.date.available,dc.date.issued,dc.description.abstract[en],dc.format.extent,dc.identifier.uri,dc.language,dc.rights.uri,dc.subject.ddc,dc.subject[en],dc.title,dc.type,dcterms.accessRights.openaire,dcterms.bibliographicCitation.articlenumber,dcterms.bibliographicCitation.doi,dcterms.bibliographicCitation.journaltitle,dcterms.bibliographicCitation.number,dcterms.bibliographicCitation.originalpublishername,dcterms.bibliographicCitation.url,dcterms.bibliographicCitation.volume,dcterms.isPartOf.eissn,refubium.affiliation,refubium.affiliation.other,refubium.resourceType.isindependentpub "19377262-bd0c-42c0-bab4-c2d8b2c6d99f","fub188/16","Schötz, Sebastian||Reisbeck, Felix||Schmitt, Ann-Cathrin||Dimde, Mathias||Quaas, Elisa||Achazi, Katharina||Haag, Rainer","2022-01-20T15:24:33Z","2022-01-20T15:24:33Z","2021","The sensitivity of therapeutic proteins is a challenge for their use in biomedical applications, as they are prone to degradation and opsonization, thus limiting their potential. This demands for the development of drug delivery systems shielding proteins and releasing them at the site of action. Here, we describe the synthesis of novel polyglycerol-based redox-responsive nanogels and report on their potential as nanocarrier systems for the delivery of cytochrome C (CC). This system is based on an encapsulation protocol of the therapeutic protein into the polymer network. NGs were formed via inverse nanoprecipitation using inverse electron-demand Diels–Alder cyclizations (iEDDA) between methyl tetrazines and norbornenes. Coprecipitation of CC led to high encapsulation efficiencies. Applying physiological reductive conditions of l-glutathione (GSH) led to degradation of the nanogel network, releasing 80% of the loaded CC within 48 h while maintaining protein functionality. Cytotoxicity measurements revealed high potency of CC-loaded NGs for various cancer cell lines with low IC50 values (up to 30 μg·mL−1), whereas free polymer was well tolerated up to a concentration of 1.50 mg·mL−1. Confocal laser scanning microscopy (CLSM) was used to monitor internalization of free and CC-loaded NGs and demonstrate the protein cargo’s release into the cytosol.","14 Seiten","https://refubium.fu-berlin.de/handle/fub188/33666||http://dx.doi.org/10.17169/refubium-33386","eng","https://creativecommons.org/licenses/by/4.0/","500 Naturwissenschaften und Mathematik::540 Chemie::540 Chemie und zugeordnete Wissenschaften||600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::615 Pharmakologie, Therapeutik","nanogels||protein delivery||iEDDA","Tunable Polyglycerol-Based Redox-Responsive Nanogels for Efficient Cytochrome C Delivery","Wissenschaftlicher Artikel","open access","1276","10.3390/pharmaceutics13081276","Pharmaceutics","8","MDPI","https://doi.org/10.3390/pharmaceutics13081276","13","1999-4923","Biologie, Chemie, Pharmazie","Institut für Chemie und Biochemie:::bdaf1c47-f341-464f-b012-0d24067d34b8:::600","no"