Peptide-like Polymers Exerting Effective Glioma-Targeted siRNA Delivery and Release for Therapeutic Application.

Abstract

Lipopolymer 49, a solid-phase synthesized T-shaped peptide-like oligoamide containing two central oleic acids, 20 aminoethane, and two terminal cysteine units, is identified as very potent and biocompatible small interfering RNA (siRNA) carrier for gene silencing in glioma cells. This carrier is combined with a novel targeting polymer 727, containing a precise sequence of Angiopep 2 targeting peptide, linked with 28 monomer units of ethylene glycol, 40 aminoethane, and two terminal cysteines in siRNA complex formation. Angiopep-polyethylene glycol (PEG)/siRNA polyplexes exhibit good nanoparticle features, effective glioma-targeting siRNA delivery, and intracellular siRNA release, resulting in an outstanding gene downregulation both in glioma cells and upon intravenous delivery in glioma model nude mice without significant biotoxicity. Therefore, this novel siRNA delivery system is expected to be a promising strategy for targeted and safe glioma therapy.

• Authors: Sai An, Dongsheng He, Ernst Wagner, Chen Jiang
• Journal: Small (Weinheim an der Bergstrasse, Germany) (Small) Vol. 11 Issue 38 Pg. 5142-50 (Oct 2015) ISSN: 1613-6829 [Electronic] Germany
• PMID: 26222334 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• BAG3 protein, human
• CY5.5 cyanine dye
• Carbocyanines
• Peptides
• Polymers
• RNA, Messenger
• RNA, Small Interfering
• Polyethylene Glycols

Topics

• Adaptor Proteins, Signal Transducing (genetics, metabolism)
• Animals
• Apoptosis Regulatory Proteins (genetics, metabolism)
• Brain (pathology)
• Brain Neoplasms (drug therapy, genetics, pathology)
• Carbocyanines (metabolism)
• Cell Line, Tumor
• Disease Models, Animal
• Down-Regulation
• Drug Delivery Systems
• Electrophoresis, Agar Gel
• Endocytosis (drug effects)
• Gene Silencing
• Gene Transfer Techniques
• Glioma (drug therapy, genetics, pathology)
• Humans
• Mice, Nude
• Nanoparticles (chemistry)
• Oxidation-Reduction
• Peptides (chemistry)
• Polyethylene Glycols (chemistry)
• Polymerase Chain Reaction
• Polymers (chemistry)
• RNA, Messenger (genetics, metabolism)
• RNA, Small Interfering (metabolism)
• Transfection