TY - JOUR
T1 - Amphiphilic poly(α)glutamate polymeric micelles for systemic administration of siRNA to tumors
AU - Krivitsky, Adva
AU - Polyak, Dina
AU - Scomparin, Anna
AU - Eliyahu, Shay
AU - Ofek, Paula
AU - Tiram, Galia
AU - Kalinski, Hagar
AU - Avkin-Nachum, Sharon
AU - Feiner Gracia, Natàlia
AU - Albertazzi, Lorenzo
AU - Satchi-Fainaro, Ronit
N1 - Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2018/2
Y1 - 2018/2
N2 - 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.
AB - 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.
KW - Amphiphilic poly(α)glutamate
KW - Anticancer therapy
KW - Cationic polymer
KW - Polyplexes
KW - siRNA systemic delivery
UR - http://www.scopus.com/inward/record.url?scp=85037537659&partnerID=8YFLogxK
U2 - 10.1016/j.nano.2017.10.012
DO - 10.1016/j.nano.2017.10.012
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C2 - 29127036
AN - SCOPUS:85037537659
SN - 1549-9634
VL - 14
SP - 303
EP - 315
JO - Nanomedicine: Nanotechnology, Biology, and Medicine
JF - Nanomedicine: Nanotechnology, Biology, and Medicine
IS - 2
ER -