{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Baumer N"],"funding":["Deutsche Forschungsgemeinschaft","Wilhelm Sander-Stiftung"],"pagination":["2210-2224"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8993695"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["41(15)"],"pubmed_abstract":["The small arginine-rich protein protamine condenses complete genomic DNA into the sperm head. Here, we applied its high RNA binding capacity for spontaneous electrostatic assembly of therapeutic nanoparticles decorated with tumour-cell-specific antibodies for efficiently targeting siRNA. Fluorescence microscopy and DLS measurements of these nanocarriers revealed the formation of a vesicular architecture that requires presence of antibody-protamine, defined excess of free SMCC-protamine, and anionic siRNA to form. Only these complex nanoparticles were efficient in the treatment of non-small-cell lung cancer (NSCLC) xenograft models, when the oncogene KRAS was targeted via EGFR-mediated delivery. To show general applicability, we used the modular platform for IGF1R-positive Ewing sarcomas. Anti-IGR1R-antibodies were integrated into an antibody-protamine nanoparticle with an siRNA specifically against the oncogenic translocation product EWS/FLI1. Using these nanoparticles, EWS/FLI1 knockdown blocked in vitro and in vivo growth of Ewing sarcoma cells. We conclude that these antibody-protamine-siRNA nanocarriers provide a novel platform technology to specifically target different cell types and yet undruggable targets in cancer therapy by RNAi."],"journal":["Oncogene"],"pubmed_title":["Targeted siRNA nanocarrier: a platform technology for cancer treatment."],"pmcid":["PMC8993695"],"funding_grant_id":["2014.054.1","DFG EXC1003","2017.071.1","EXC1003"],"pubmed_authors":["Tiemann J","Gumnior A","Strassert CA","Brand C","Dersch P","Greune L","Peipp M","Rossig C","Koeffler HP","Suburu MEG","Neri D","Baumer N","Kellmann N","Meyer T","Berdel WE","Baumer S","Scheller A","Muller-Tidow C","Ruter C","Wittmann L","Hartmann W","Lenz G"],"additional_accession":[]},"is_claimable":false,"name":"Targeted siRNA nanocarrier: a platform technology for cancer treatment.","description":"The small arginine-rich protein protamine condenses complete genomic DNA into the sperm head. Here, we applied its high RNA binding capacity for spontaneous electrostatic assembly of therapeutic nanoparticles decorated with tumour-cell-specific antibodies for efficiently targeting siRNA. Fluorescence microscopy and DLS measurements of these nanocarriers revealed the formation of a vesicular architecture that requires presence of antibody-protamine, defined excess of free SMCC-protamine, and anionic siRNA to form. Only these complex nanoparticles were efficient in the treatment of non-small-cell lung cancer (NSCLC) xenograft models, when the oncogene KRAS was targeted via EGFR-mediated delivery. To show general applicability, we used the modular platform for IGF1R-positive Ewing sarcomas. Anti-IGR1R-antibodies were integrated into an antibody-protamine nanoparticle with an siRNA specifically against the oncogenic translocation product EWS/FLI1. Using these nanoparticles, EWS/FLI1 knockdown blocked in vitro and in vivo growth of Ewing sarcoma cells. We conclude that these antibody-protamine-siRNA nanocarriers provide a novel platform technology to specifically target different cell types and yet undruggable targets in cancer therapy by RNAi.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Apr","modification":"2025-04-05T00:29:14.641Z","creation":"2025-04-05T00:29:14.641Z"},"accession":"S-EPMC8993695","cross_references":{"pubmed":["35220407"],"doi":["10.1038/s41388-022-02241-w"]}}