Enhanced Transfection Efficiency and Targeted Delivery of Self-assembling H-R3-dendriplexes in EGFR-overexpressing Tumor Cells

Overview

Journal Oncotarget

Specialty Oncology

Date 2015 Aug 27

PMID 26309162

Citations 2

Authors

Jun Li

Shengnan Li

Songyun Xia

Jinfeng Feng

Xuedi Zhang

Yanli Hao

Lei Chen

Xiaoning Zhang

Affiliations

Soon will be listed here.

Abstract

The efficient gene transfection, cellular uptake and targeted delivery in vivo are key issues for non-viral gene delivery vectors in cancer therapy. To solve these issues, we designed a new targeted gene delivery system based on epidermal growth factor receptor (EGFR) targeting strategy. An anti-EGFR monoclonal antibody h-R3 was introduced to dendriplexes of PAMAM and DNA via electrostatic interactions to form self-assembled h-R3-PAMAM-DNA complexes (h-R3-dendriplexes). Dendriplexes h-R3-dendriplexes represented excellent DNA encapsulation ability and formed unique nanostructures. Compared to dendriplexes, h-R3-dendriplexes presented lower cytotoxicity, higher gene transfection efficiency, excellent endosome escape ability and high nuclear accumulation in the EGFR-overexpressing HepG2 cells. Both ex vivo fluorescence imaging and confocal results of frozen section revealed that h-R3-dendriplexes showed higher targeted delivery and much better gene expression in the tumors than dendriplexes at the same N/P ratio, and h-R3-dendriplexes had accumulation primarily in the tumor and kidney. Moreover, h-R3-dendriplexes for p53 delivery indicated efficient cell growth inhibition and potentiated paclitaxel-induced cell death. These results indicate that the h-R3-dendriplexes represent a great potential to be used as efficient targeted gene delivery carriers in EGFR-overexpressing tumor cells.

Citing Articles

A folate receptor-targeted lipoplex delivering interleukin-15 gene for colon cancer immunotherapy.

Liang X, Luo M, Wei X, Ma C, Yang Y, Shao B Oncotarget. 2016; 7(32):52207-52217.

PMID: 27438147 PMC: 5239545. DOI: 10.18632/oncotarget.10537.

Antibody h-R3-dendrimer mediated siRNA has excellent endosomal escape and tumor targeted delivery ability, and represents efficient siPLK1 silencing and inhibition of cell proliferation, migration and invasion.

Li J, Liu J, Li S, Hao Y, Chen L, Zhang X Oncotarget. 2016; 7(12):13782-96.

PMID: 26883109 PMC: 4924678. DOI: 10.18632/oncotarget.7368.

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