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

Adva Krivitsky, Dina Polyak, Anna Scomparin, Shay Eliyahu, Paula Ofek, Galia Tiram, Hagar Kalinski, Sharon Avkin-Nachum, Natàlia Feiner Gracia, Lorenzo Albertazzi, Ronit Satchi-Fainaro*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

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 ~50 nm 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 or spleen. Nevertheless, the polyplexes failed to induce specific mRNA degradation, hence neither reduction in tumor volume nor prolonged mice survival was seen.

Original languageEnglish
Pages (from-to)303-315
Number of pages13
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume14
Issue number2
DOIs
StatePublished - Feb 2018

Funding

FundersFunder number
AXA Research Fund
Office of the Chief Scientist of the Israel Ministry of Industry, Trade and Labor
Ministerio de Economía y Competitividad
European Research Council
Ministerio de Economía, Industria y Competitividad, Gobierno de España
European Regional Development Fund
Seventh Framework Programme617445
Seventh Framework ProgrammeFP/2007-2013
Generalitat de CatalunyaSAF2016-75241-R

    Keywords

    • Amphiphilic poly(α)glutamate
    • Anticancer therapy
    • Cationic polymer
    • Polyplexes
    • siRNA systemic delivery

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