Biodistribution and Targeted Antitumor Effects of Trastuzumab-Modified Gold Nanorods in Mice with Gastric Cancer

Abstract

Background and Objectives: Targeted drug is often engulfed and cleared by the reticuloendothelial system in vivo, resulting in reduced treatment efficacy. This study aimed to explore the biodistribution and HER-2-targeted antitumor effects of trastuzumab-modified gold nanorods (Tra-AuNRs) in a gastric cancer animal model. Methods: Gold nanorods were synthesized using a seed-mediated growth method, and then subjected to trastuzumab-targeted modification. Elemental analysis, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy were performed; UV–visible absorption peak, photothermal effects, morphology, and size distribution of Tra-AuNRs were characterized. The targeted killing effect of Tra-AuNRs on gastric cancer cells was assessed in vitro. Tra-AuNRs were injected intravenously and intratumorally into gastric cancer-bearing nude mice in vivo and their distribution was detected. Tumor growth inhibition rate and tumor apoptosis-related protein expression were compared between groups. Results: Tra-AuNRs presented a relatively uniform morphology with an average particle size of 59.9 nm and a longitudinal plasmon resonance absorption peak of 790 nm. The targeted killing rate of gastric cancer cells in vitro by Tra-AuNRs was 87.9%. After intravenous injection, Tra-AuNRs were mainly distributed in the liver, tumor, spleen, and lungs. Comparatively, Tra-AuNRs were mainly distributed in the tumor when intratumorally injected, with a tumor concentration of 6.42 µg/g after 24 h. The tumor growth inhibition rate reached 78.3% in the intratumoral injection group, with significantly higher BAX, BAD, and CASPASE-3 expression than that in the intravenous injection group. Conclusion: The findings suggest that Tra-AuNRs can be used for HER-2-positive gastric cancer treatment. Intratumoral injection of Tra-AuNRs significantly increased the local tumor drug concentration and improved the molecular targeted antitumor growth effect in gastric cancer-bearing nude mice.