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

Abstract

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-Fe 3 O 4 -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-Fe 3 O 4 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-Fe 3 O 4 -Herceptin was verified in a subcutaneous xenograft mouse model containing SGC-7901 cells via detecting aggregated low intensity in T 2 -weighted magnetic resonance imaging, which was further confirmed by immunohistochemistry. Therefore, oxaliplatin-Au-Fe 3 O 4 -Herceptin is a promising multifunctional platform for simultaneous magnetic traceable and HER2 targeted chemotherapy for gastric cancer.

An overview and bibliometric analysis on the colorectal cancer therapy by magnetic functionalized nanoparticles for the responsive and targeted drug delivery

“…The first attempt in vivo utilizing MNPs as a carrier for Oxaliplatin was performed to improve the colon cancer treatment responses by Liu et al [ 108 ]. It was demonstrated that Au-Fe 3 O 4 -Herceptin MNPs as a carrier for Oxaliplatin acted as dual-functional NPs conjugated and could oxaliplatin delivery and human epithelial growth factor receptor 2 targetings (HER2).…”

Recent Advances in the Use of Iron–Gold Hybrid Nanoparticles for Biomedical Applications

“…The nanocomposite has probes for mass spectroscopy and nuclear magnetic resonance imaging as well as a drug-release assay that releases oxaliplatin (a breast cancer drug) in an acidic medium. The pH-controlled drug release lowers the dosage and period of administration for patients, thus reducing side effects and build-up of drug resistance in patients [ 135 ].…”

Nanotechnology-based strategies for gastric cancer imaging and treatment

“…Other HER2 targeting strategies were also proposed in the nanotechnology realm. [28][29][30][31][32] Christopher et al reported dual HER2 targeting nanoparticles with trastuzumab and liposomal-encapsulated doxorubicin (MM-302) demonstrated synergistic targeting and anti-tumor activity in breast cancer and gastric cancer. 33 By targeting different domains of the HER2 receptor, MM-302 and trastuzumab could simultaneously bind to HER2-overexpressing tumor cells.…”