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

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.