Antibody-nanoparticle conjugate constructed with trastuzumab 
and nanoparticle albumin-bound paclitaxel for targeted
 therapy of human epidermal growth factor receptor 2-positive gastric cancer

Xiong,Jian; Han,Shuhua; Ding,Shuang; He,Jingchao; Zhang,Haijun

doi:10.3892/or.2018.6201

Antibody-nanoparticle conjugate constructed with trastuzumab and nanoparticle albumin-bound paclitaxel for targeted therapy of human epidermal growth factor receptor 2-positive gastric cancer

Authors:
- Jian Xiong
- Shuhua Han
- Shuang Ding
- Jingchao He
- Haijun Zhang
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Affiliations: Department of Oncology, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China, Department of Respiration, Zhongda Hospital, Medical School of Southeast University, Nanjing, Jiangsu 210009, P.R. China
Published online on: January 9, 2018 https://doi.org/10.3892/or.2018.6201
Pages: 1396-1404

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Abstract

Gastric cancer (GC) is the most lethal malignancy in the digestive system. This study investigated an antibody-nanoparticle conjugate (ANC) constructed with trastuzumab (Herceptin®) and nanoparticle albumin-bound paclitaxel (nab-paclitaxel, Abraxane®) (trastuzumab/nab‑paclitaxel) as a novel strategy of targeted therapy for human epidermal growth factor receptor 2 (HER2) positive GC. The ANC was fabricated with trastuzumab and nab‑paclitaxel by a ‘one-step’ synthesis using EDC/NHS. In vitro antitumor efficacy was evaluated by cell viability, apoptosis rate and cell cycle of HER2-positive GC NCI‑N87 cells and compared with paclitaxel (Taxol®), nab‑paclitaxel and trastuzumab/nab‑paclitaxel. In addition, GC xenograft models were established to evaluate antitumor efficacy in vivo. These results demonstrated that trastuzumab/nab‑paclitaxel was spherical with a suitable size (139.18±32.06 nm). The half-maximal inhibitory concentration (IC50) for NCI‑N87 cells was 0.24±0.08, 0.13±0.03 and 0.048±0.01 µg/ml of paclitaxel, nab‑paclitaxel and trastuzumab/nab‑paclitaxel, respectively. Compared with paclitaxel and nab‑paclitaxel, trastuzumab/nab‑paclitaxel could induce a higher rate of apoptosis and significant G2/M arrest. At 4 weeks after treatment, tumor-bearing mice had a mean tumor volume of 233±24 mm3 treated by trastuzumab/nab‑paclitaxel, 559±97 mm3 by nab‑paclitaxel, 871±94 mm3 by paclitaxel and 1,576±190 mm3 by PBS as control, respectively, which showed that trastuzumab/nab‑paclitaxel could surpass nab‑paclitaxel and paclitaxel in antitumor effect. Furthermore, the NIR imaging indicated that trastuzumab/nab‑paclitaxel labeled by NIR-797 could more precisely focus on tumor regions. In conclusion, trastuzumab/nab‑paclitaxel could mediate targeted therapy and enhance antitumor efficacy, which could represent a novel therapeutic agent for HER2‑positive GC.

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