Targeted siRNA nanocarrier: a platform technology for cancer treatment

Bäumer, N.; Tiemann, J.; Scheller, A.; Meyer, T.; Wittmann, L.; Gutierrez Suburu, M. E.; Greune, L.; Peipp, M.; Kellmann, N.; Gumnior, A.; Brand, C.; Hartmann, W.; Rossig, C.; Müller-Tidow, C.; Neri, D;, Strassert, C. A.; Rüter, C.; Dersch, P.; Lenz, G.; Koeffler, H. P.; Berdel, W. E.; Bäumer, S.

Research article (journal)

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.

Details zur Publikation

Release year: 2022
Language in which the publication is written: English
Link to the full text: https://rdcu.be/cPx43