Antitumoral Cascade-Targeting Ligand for IL-6 Receptor-Mediated Gene Delivery to Glioma

Molecular Therapy : the Journal of the American Society of Gene Therapy
Shanshan WangRongqin Huang

Abstract

The effective treatment of glioma is largely hindered by the poor transfer of drug delivery systems across the blood-brain barrier (BBB) and the difficulty in distinguishing healthy and tumorous cells. In this work, for the first time, an interleukin-6 receptor binding I6P7 peptide was exploited as a cascade-targeting ligand in combination with a succinoyl tetraethylene pentamine (Stp)-histidine oligomer-based nonviral gene delivery system (I6P7-Stp-His/DNA). The I6P7 peptide provides multiple functions, including the cascade-targeting potential represented by a combined BBB-crossing and subsequent glioma-targeting ability, as well as a direct tumor-inhibiting effect. I6P7-Stp-His/DNA nanoparticles (NPs) mediated higher gene expression in human glioma U87 cells than in healthy human astrocytes and a deeper penetration into glioma spheroids than scrambled peptide-modified NPs. Transport of I6P7-modified, but not the control, NPs across the BBB was demonstrated in vitro in a transwell bEnd.3 cell model resulting in transfection of underlying U87 cells and also in vivo in glioma-bearing mice. Intravenous administration of I6P7-Stp-His/plasmid DNA (pDNA)-encoding inhibitor of growth 4 (pING4) significantly prolonged the survival ti...Continue Reading

Citations

Jun 20, 2017·Molecular Therapy : the Journal of the American Society of Gene Therapy·S Moein Moghimi, Ernst Wagner
Apr 14, 2019·The Journal of Gene Medicine·Shanshan Wang, Rongqin Huang
May 16, 2019·Chemical Society Reviews·Wei TangXiaoyuan Chen
May 30, 2020·Acta Pharmacologica Sinica·Sumaira HanifBing-Yang Shi
Apr 5, 2019·Journal of Nanobiotechnology·Magdalena Bamburowicz-KlimkowskaIreneusz P Grudzinski
Oct 1, 2017·Bioscience Reports·Ana Krhac LevacicErnst Wagner
Sep 24, 2020·Pharmaceutics·Yanfang Wang, Ernst Wagner
Nov 11, 2020·Drug Development Research·Selvaraj KunjiappanPanneerselvam Theivendren
Apr 5, 2020·Advanced Drug Delivery Reviews·Franziska Freitag, Ernst Wagner
Oct 19, 2020·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jie LuoErnst Wagner
Dec 20, 2020·Biochemical and Biophysical Research Communications·Yukio TakamoriTakashi Kawakami
Jun 7, 2021·International Journal of Pharmaceutics·Marcela Tavares LuizMarlus Chorilli
Oct 30, 2021·The Journal of Gene Medicine·Songhui XuA James Mixson

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