4.8 Article

Targeted siRNA nanocarrier: a platform technology for cancer treatment

Journal

ONCOGENE
Volume 41, Issue 15, Pages 2210-2224

Publisher

SPRINGERNATURE
DOI: 10.1038/s41388-022-02241-w

Keywords

-

Funding

  1. Deutsche Krebshilfe [70112282]
  2. Wilhelm Sander-Stiftung [2014.054.1, 2017.071.1]
  3. Innovative Medical Research of the University of Munster Medical School [111418, 211502, 121314, 111501, 121802]
  4. Cedars-Sinai Cancer (CSC) Developmental Funds
  5. Deutsche Forschungsgemeinschaft [6103/3-1, DFG CRC1009B03, DFG EXC1003]
  6. Interdisciplinary Centre for Clinical Research (IZKF Munster) [Bau2/009/19]
  7. Sanford Burnham Prebys (SBP) Cancer Center

Ask authors/readers for more resources

A study found that the small arginine-rich protein protamine can condense genomic DNA into the sperm head, and its high RNA binding capacity can be utilized for the spontaneous electrostatic assembly of therapeutic nanoparticles decorated with tumor-cell-specific antibodies for efficient targeting of siRNA. These nanoparticles showed promising results in treating non-small-cell lung cancer and Ewing sarcoma models.
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.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available