Development of a library of polymeric nanocarriers for the selective delivery of oligonucleotides to tumors
We published a successful novel approach using biocompatible polyglycerol dendrimers (with Rainer Haag’s group) and polyaminated polyglutamic acid for parenteral delivery of siRNA and microRNA to tumors eliminating the need to know the tumor location. Ongoing experiments show that, using this unique platform technology as a RNAi nanocarrier, we were able to suppress brain tumor growth and significantly increase the time to progression and survival of orthotopic glioblastoma-bearing mice. This unprecedented inhibition of high-grade glioblastoma by targeting its downstream effectors and inhibiting cells proliferation and migration, suggests a key role for these anticancer miRNAs in gliomas. Our results also suggest that this anticancer polyplex could serve as a potential therapeutic agent for untreatable and temozolomide-resistant brain tumors. Efforts were also focused on using the polyaminated polyglutamic acid polymeric nanocarriers for the delivery of several siRNAs/microRNAs for ovarian carcinoma, breast cancer adenocarcinoma and osteosarcoma. These projects were a part of a Magneton collaboration with Rosetta Genomics (polyglycerol) and of MAGNET Rimonim Consortium with QBI and Rosetta Genomics (polyglutamic acid).
Internalization of Aminated Poly(alpha)glutamate (APA) complexed with Cy5-siRNA (red) into cells. The nucleus is stained with DAPI and actin filaments are stained with FITC-labeled Phalloidin.
- Ofek P, Fischer W, Calderón M, Haag R and Satchi-Fainaro R, In vivo delivery of small interfering RNA to tumors and their vasculature by novel dendritic nanocarriers, FASEB Journal, 24(9), 3122-3134 (2010). [PDF] [PubMed]
- Shatsberg Z, et al., (Satchi-Fainaro R), Functionalized nanogels carrying an anticancer microRNA for glioblastoma therapy, Journal of Controlled Release, 239:159-68 (2016). [PDF] [PubMed]
- Polyak D*, Krivitsky A*, Scomparin A*, et al., (Satchi-Fainaro R), Systemic delivery of siRNA by aminated poly(α)glutamate for the treatment of solid tumors, Journal of Controlled Release, 257:132-143 (2017). [PDF] [PubMed]
- Krivitsky A*, Polyak D*, Scomparin A*, et al., (Satchi-Fainaro R), Amphiphilic poly(α)glutamate polymeric micelles for systemic administration of siRNA to tumors. Nanomedicine 14(2):303-315, (2017). [PDF] [PubMed]