T7 peptide-functionalized nanoparticles utilizing RNA interference for glioma dual targeting.

Abstract

Among all the malignant brain tumors, glioma is the deadliest and most common form with poor prognosis. Gene therapy is regarded as a promising way to halt the progress of the disease or even cure the tumor and RNA interference (RNAi) stands out. However, the existence of the blood-brain barrier (BBB) and blood tumor barrier (BTB) limits the delivery of these therapeutic genes. In this work, the delivery system targeting to the transferrin (Tf) receptor highly expressed on both BBB and glioma was successfully synthesized and would not compete with endogenous Tf. U87 cells stably express luciferase were employed here to simulate tumor and the RNAi experiments in vitro and in vivo validated that the gene silencing activity was 2.17-fold higher with the targeting ligand modification. The dual-targeting gene delivery system exhibits a series of advantages, such as high efficiency, low toxicity, stability and high transaction efficiency, which may provide new opportunities in RNAi therapeutics and nanomedicine of brain tumors.

• Authors: Yuyang Kuang, Sai An, Yubo Guo, Shixian Huang, Kun Shao, Yang Liu, Jianfeng Li, Haojun Ma, Chen Jiang
• Journal: International journal of pharmaceutics (Int J Pharm) Vol. 454 Issue 1 Pg. 11-20 (Sep 15 2013) ISSN: 1873-3476 [Electronic] Netherlands
• PMID: 23867728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Crown Copyright © 2013. Published by Elsevier B.V. All rights reserved.

Chemical References

• Dendrimers
• Ligands
• Oligopeptides
• RNA, Small Interfering
• Receptors, Transferrin
• Polylysine
• Polyethylene Glycols

Topics

• Animals
• Biological Transport
• Blood-Brain Barrier (metabolism)
• Brain Neoplasms (genetics, metabolism, pathology, therapy)
• Capillary Permeability
• Cell Line, Tumor
• Dendrimers (chemistry)
• Gene Transfer Techniques
• Genetic Therapy (methods)
• Glioma (genetics, metabolism, pathology, therapy)
• Humans
• Ligands
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred ICR
• Mice, Nude
• Nanoparticles
• Nanotechnology
• Oligopeptides (chemistry, metabolism)
• Polyethylene Glycols (chemistry)
• Polylysine (chemistry)
• RNA Interference
• RNA, Small Interfering (metabolism)
• Receptors, Transferrin (metabolism)
• Time Factors
• Xenograft Model Antitumor Assays