Target‑specific delivery of oxaliplatin to HER2‑positive gastric cancer cells in vivo using oxaliplatin‑au‑fe3o4‑herceptin nanoparticles

Liu,Daren; Li,Xiaowen; Chen,Changlei; Li,Chao; Zhou,Chuanbiao; Zhang,Weidong; Zhao,Jiangang; Fan,Jie; Cheng,Kai; Chen,Li

doi:10.3892/ol.2018.8323

Target‑specific delivery of oxaliplatin to HER2‑positive gastric cancer cells in vivo using oxaliplatin‑au‑fe3o4‑herceptin nanoparticles

Authors:
- Daren Liu
- Xiaowen Li
- Changlei Chen
- Chao Li
- Chuanbiao Zhou
- Weidong Zhang
- Jiangang Zhao
- Jie Fan
- Kai Cheng
- Li Chen
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Affiliations: Department of General Surgery, Second Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China, Key Laboratory of Applied Chemistry of Zhejiang, Department of Chemistry, Zhejiang University, Hangzhou, Zhejiang 310009, P.R. China, Molecular Imaging Program, Canary Center for Cancer Early Detection, Department of Radiology and Bio‑X Program, Stanford University, Stanford, CA 94305, USA
Published online on: March 22, 2018 https://doi.org/10.3892/ol.2018.8323
Pages: 8079-8087

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Abstract

Gastric cancer is the fourth most common malignancy globally. In order to decrease the dosage and side effects of conventional chemotherapy, and achieve improved benefits from molecular targeted therapy, novel drug delivery systems were developed in the present study. Oxaliplatin‑Au‑Fe3O4‑Herceptin® acts as a dual‑functional nanoparticles (NPs) conjugate and possesses the capability of human epithelial growth factor receptor 2 (HER2) targeting and oxaliplatin delivery. The 8‑20 nm Au‑Fe3O4 were synthesized by decomposing iron pentacarbonyl on the surfaces of Au NPs in the presence of oleic acid and oleylamine. Following being coated with polyethylene glycol, the NPs possessed a ζ‑potential of 13.8±1.6 mV and were demonstrated to exhibit no cytotoxicity when Fe concentration is <100 µg/ml via an MTS assay. Mass spectrometry analysis detected a peak at m/z 148,000, and Nuclear Magnetic Resonance indicated peaks at δ 3.51 (8.00H, s, 3‑H), 2.97‑3.02 (3.80H, t, 2‑H) and 2.72‑2.76 (3.72H, t, 1‑H) following successful loading with Herceptin and oxaliplatin probes. A drug release assay via dialysis cassettes demonstrated that 25% of the oxaliplatin was released at pH 8.0, however >58% was released at pH 6.0 following 4 h incubation, indicating its pH‑dependent release characteristic. The active targeting feature of oxaliplatin‑Au‑Fe3O4‑Herceptin was verified in a subcutaneous xenograft mouse model containing SGC‑7901 cells via detecting aggregated low intensity in T2‑weighted magnetic resonance imaging, which was further confirmed by immunohistochemistry. Therefore, oxaliplatin‑Au‑Fe3O4‑Herceptin is a promising multifunctional platform for simultaneous magnetic traceable and HER2 targeted chemotherapy for gastric cancer.

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