Improvement of Targeted Gene Delivery to Human Cancer Cells by a Novel Trifunctional Crosslinker

Abstract

A facile method for the construction of an immunoconjugate which displays targeting ligands, such as antibody fragments, with a high density is reported. For this purpose, we synthesized a novel trifunctional crosslinking reagent. By the use of this reagent, ligands targeting the specific cell can be displayed on the surface of the drug carrier with a high density. In this study, we display HER2 (human epidermal growth-factor receptor-2) binding ligands on branched polyethylenimine (PEI), which can form polyplexes with plasmid DNA. Kinetic analysis of the binding to the extracellular domain of HER2 show the PEI displaying a high density of ligands binds to the target more strongly compared to the PEI displaying ligands at a low density. The increased density of HER2 ligands displayed on the gene carrier contributes to the improved transfection efficiency. This approach can be applied to other drug delivery systems, including liposome, micelle, and so on.

Applications of immunochemistry in human health: advances in vaccinology and antibody design (IUPAC Technical Report)

“…Several ligands binding to cell surface receptors have been targeted for DNA delivery. Such receptors include those for mannose, low-density lipoprotein, transferrin, neurotensin, asialoglycoprotein, C-type lectin, and chemokine receptor [105][106][107][108][109].…”

Efficient Gene Delivery by EGF-Lipoplexes In Vitro and In Vivo

“…On the other hand, EGFR-targeted gene delivery with nonviral vectors has been reported in several works. In the majority, they used polyplexes containing polylisine (PLL [25][26][27]), polyethylenimine (PEI [28,29]), or EGF attached to lipoplexes by a covalent or noncovalent bond, as vectors [11,30]. In this study, we wanted to design a fast, simple and reliable method based on lipoplexes, which are widely used as delivery systems [31].…”