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Int. J. Mol. Sci. 2017, 18(10), 2029; doi:10.3390/ijms18102029

Targeted Delivery of siRNA with pH-Responsive Hybrid Gold Nanostars for Cancer Treatment

School of Pharmacy, Nantong University, Nantong 226001, China
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Received: 7 September 2017 / Revised: 18 September 2017 / Accepted: 18 September 2017 / Published: 22 September 2017
(This article belongs to the Collection Bioactive Nanoparticles)
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Abstract

In this work, we report the engineering of gold nanostars (GNS) to deliver small interfering RNA (siRNA) into HepG2 cells. The ligand DG-PEG-Lipoic acid (LA)-Lys-9R (hydrazone) was designed to functionalize GNS, and create the nanoparticles named as 9R/DG-GNS (hydrazone). In the ligand, 2-deoxyglucose (DG) is the targeting molecule, polyethylene glycol (PEG) helps to improve the dispersity and biocompatibility, 9-poly-d-arginine (9R) is employed to provide a positive surface charge and adsorb negative siRNA, and hydrazone bonds are pH-responsive and can avoid receptor-mediated endosomal recycling. Compared to GNS alone, 9R/DG-GNS (hydrazone) showed superior transfection efficiency. The expressions of cyclooxygenase-2 (COX-2) in HepG2 and SGC7901 cells were significantly suppressed by siRNA/9R/DG-GNS (hydrazone) complex. Notably, 9R/DG-GNS (hydrazone) possessed low cytotoxicity even at high concentrations in both normal cells and tumor cells. The combination treatment of siRNA/9R/DG-GNS (hydrazone) complex inhibited the cell growth rate by more than 75%. These results verified that the pH-responsive GNS complex is a promising siRNA delivery system for cancer therapy, and it is anticipated that near-infrared absorbing GNS with good photothermal conversion efficiency can be potentially used for photothermal therapy of tumors. View Full-Text
Keywords: gold nanostars; targeted delivery; siRNA; cancer treatment; cyclooxygenase-2; gene silence gold nanostars; targeted delivery; siRNA; cancer treatment; cyclooxygenase-2; gene silence
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Zhu, H.; Liu, W.; Cheng, Z.; Yao, K.; Yang, Y.; Xu, B.; Su, G. Targeted Delivery of siRNA with pH-Responsive Hybrid Gold Nanostars for Cancer Treatment. Int. J. Mol. Sci. 2017, 18, 2029.

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