Oncotarget

Research Papers:

Enhanced transfection efficiency and targeted delivery of self-assembling h-R3-dendriplexes in EGFR-overexpressing tumor cells

Jun Lia, Shengnan Li, Songyun Xia, Jinfeng Feng, Xuedi Zhang, Yanli Hao _, Lei Chen and Xiaoning Zhang

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Oncotarget. 2015; 6:26177-26191. https://doi.org/10.18632/oncotarget.4614

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Abstract

Jun Li1, Shengnan Li2,3, Songyun Xia3, Jinfeng Feng1, Xuedi Zhang1, Yanli Hao1, Lei Chen2,3, Xiaoning Zhang1,4

1School of Medicine, Tsinghua University, Beijing 100084, China

2The third Clinical College, Southern Medical University, Guangzhou 510515, China

3Department of gynaecology and obstetrics, PLA Navy General Hospital, Beijing 100037, China

4Collaborative Innovation Center for Biotherapy, Tsinghua University, Beijing 100084, China

Correspondence to:

Yanli Hao, e-mail: [email protected]

Lei Chen, e-mail: [email protected]

Xiaoning Zhang, e-mail: [email protected]

Keywords: h-R3, EGFR, gene therapy, PAMAM, targeted delivery

Received: February 24, 2015     Accepted: July 10, 2015     Published: July 20, 2015

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.


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