Nanomedicine
Nanomedicine
5 years ago

Amphiphilic poly(α)glutamate polymeric micelles for systemic administration of siRNA to tumors.

Sharon Avkin-Nachum, Adva Krivitsky, Lorenzo Albertazzi, Ronit Satchi-Fainaro, Shay Eliyahu, Paula Ofek, Hagar Kalinski, Dina Polyak, Galia Tiram, Anna Scomparin, Natàlia Feiner Gracia
RNAi therapeutics carried a great promise to the area of personalized medicine: the ability to target "undruggable" oncogenic pathways. Nevertheless, their efficient tumor targeting via systemic administration had not been resolved yet. Amphiphilic alkylated poly(α)glutamate amine (APA) can serve as a cationic carrier to the negatively-charged oligonucleotides. APA polymers complexed with siRNA to form round-shaped, homogenous and reproducible nano-sized polyplexes bearing ~50nm size and slightly negative charge. In addition, APA:siRNA polyplexes were shown to be potent gene regulators in vitro. In light of these preferred physico-chemical characteristics, their performance as systemically-administered siRNA nanocarriers was investigated. Intravenously-injected APA:siRNA polyplexes accumulated selectively in tumors and did not accumulate in the lungs, heart, liver nor spleen. Nevertheless, the polyplexes failed to induce specific mRNA degradation, hence neither reduction in tumor volume nor prolonged mice survival were seen.

Publisher URL: http://doi.org/10.1016/j.nano.2017.10.012

DOI: 10.1016/j.nano.2017.10.012

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