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 1 , Jing Liu 2 , Shengnan Li 3 , Yanli Hao 1 , Lei Chen 3 , Xiaoning Zhang 1, 2 1 School of Medicine, Tsinghua University, Beijing 100084, China 2 Collaborative Innovation Center for Biotherapy, Tsinghua University, Beijing 100084, China 3 Department of Gynaecology and Obstetrics, PLA Navy General Hospital, Beijing 100037, China Correspondence to: Xiaoning Zhang, e-mail: drugman@tsinghua.edu.cn Keywords: siRNA delivery, h-R3, EGFR, siPLK1, targeted delivery Received: November 07, 2015      Accepted: February 05, 2016      Published: February 13, 2016 ABSTRACT 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.