Research Papers:

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

Jun Li, Jing Liu, Shengnan Li, Yanli Hao, Lei Chen and Xiaoning Zhang _

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Oncotarget. 2016; 7:13782-13796. https://doi.org/10.18632/oncotarget.7368

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Jun Li1, Jing Liu2, Shengnan Li3, Yanli Hao1, Lei Chen3, Xiaoning Zhang1,2

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

2Collaborative Innovation Center for Biotherapy, Tsinghua University, Beijing 100084, China

3Department of Gynaecology and Obstetrics, PLA Navy General Hospital, Beijing 100037, China

Correspondence to:

Xiaoning Zhang, e-mail: [email protected]

Keywords: siRNA delivery, h-R3, EGFR, siPLK1, targeted delivery

Received: November 07, 2015     Accepted: February 05, 2016     Published: February 13, 2016


The major obstacle to developing siRNA delivery is their extracellular and intracellular barriers. Herein, a humanized anti-EGFR monoclonal antibody h-R3 was developed to modify the self-assembled binary complexes (dendriplexes) of PAMAM and siRNA via electrostatic interactions, and two common ligands HSA and EGF were used as a control. Compared to dendriplexes, h-R3/EGF/HSA-dendriplexes showed increased particle size, decreased zeta potentials and lower cytotoxicity. Moreover, h-R3-dendriplexes presented greater cellular uptake and excellent endosomal escape ability in HepG2 cells. Ex vivo fluorescence imaging revealed that h-R3-dendriplexes showed higher targeted delivery and gene expression in the tumors than dendriplexes, HSA-dendriplexes and EGF-dendriplexes, which was in agreement with confocal results of cryosections. Furthermore, h-R3-dendriplexes for siPLK1 delivery indicated efficient gene silencing, potentiated cell growth inhibition and cell apoptosis, and suppressed cellular migration/invasion. These results indicate that h-R3-dendriplexes represent a great potential to be used as efficient targeted siRNA delivery carriers.

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