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
  • View Affiliations

  • 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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March-2018
Volume 39 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Xiong J, Han S, Ding S, He J and Zhang H: Antibody-nanoparticle conjugate constructed with trastuzumab and nanoparticle albumin-bound paclitaxel for targeted therapy of human epidermal growth factor receptor 2-positive gastric cancer. Oncol Rep 39: 1396-1404, 2018.
APA
Xiong, J., Han, S., Ding, S., He, J., & Zhang, H. (2018). Antibody-nanoparticle conjugate constructed with trastuzumab and nanoparticle albumin-bound paclitaxel for targeted therapy of human epidermal growth factor receptor 2-positive gastric cancer. Oncology Reports, 39, 1396-1404. https://doi.org/10.3892/or.2018.6201
MLA
Xiong, J., Han, S., Ding, S., He, J., Zhang, H."Antibody-nanoparticle conjugate constructed with trastuzumab and nanoparticle albumin-bound paclitaxel for targeted therapy of human epidermal growth factor receptor 2-positive gastric cancer". Oncology Reports 39.3 (2018): 1396-1404.
Chicago
Xiong, J., Han, S., Ding, S., He, J., Zhang, H."Antibody-nanoparticle conjugate constructed with trastuzumab and nanoparticle albumin-bound paclitaxel for targeted therapy of human epidermal growth factor receptor 2-positive gastric cancer". Oncology Reports 39, no. 3 (2018): 1396-1404. https://doi.org/10.3892/or.2018.6201