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The exponentially increased use of gold nanoclusters in diagnosis and treatment has raised serious concern about their potential threat to living organisms. However, the mechanisms of toxicity of gold nanoclusters in vitro and in vivo remain poorly understood. In this work, comparative toxicity studies, including biodistribution and excretion, were carried out with mildly and chemically synthesized ultra-small L-histidine-protected and bovine serum albumin (BSA)-protected gold nanoclusters in an all-aqueous process. These nanoclusters did not induce a remarkable impact on cell viability, even at relatively high concentrations (100 μg/mL). The haemolytic assay demonstrated that the gold nanoclusters could not destroy blood cell at 600 μg/mL. After intravenous injection with mice, the biocompatibility, biodistribution, and excretion were determined. Quantitative analysis results showed that accumulation varied in the liver, spleen, kidney, and lung, though primarily in the liver and spleen. They were excreted in urine and faeces, but mainly excreted through urine. In our study, no obvious abnormalities were found in body weight, behavioral changes, blood and serum biochemical indicators, and histopathology. These findings suggested that both gold nanoclusters showed similar effects in vivo and were safe and biocompatible, laying the foundation for safe biomedical application in the future.

Due to extensive metastasis, poor blood supply, and drug-resistant, there is still no effective clinical means to treat peritoneal dissemination of gastric cancer. Here, an aptamer-siRNA chimera (Chim)/polyethyleneimine (PEI)/5-fluorouracil (5-FU)/carbon nanotube (CNT)/collagen membrane is constructed, which could be divided into 15 layers with a thickness of 70-100 µm. Sustained release experiments show that the collagen membranes can control 5-FU release for more than 2 weeks. Aptamer-siRNA chimera can specifically bind to gastric cancer cells, enabling targeted delivery of 5-FU and silencing drug-resistant gene. In vitro experiments demonstrated that Chim/PEI/5-FU/CNT nanoparticles promoted the apoptosis of 5-FU-resistant gastric cancer cells, inhibited their invasion and proliferation. Animal experiments show that Chim/PEI/5-FU/CNT/collagen membrane significantly inhibits the expression of mitogen-activated protein kinase (MAPK), and effectively treats peritoneal dissemination of 5-FU-resistant gastric cancer. Compared with siRNA/PEI/5-FU/CNT group, ki-67 proliferation index, and matrix metallopeptidase 9 (MMP9) expression are significantly decreased in the Chim/PEI/5-FU/CNT group, while the proportion of apoptotic cells is markly increased. In conclusion, a chimera/PEI/5-FU/CNT/collagen membrane is constructed, which can effectively treat peritoneal dissemination of drug-resistant gastric cancer. The study provides a new therapeutic approach for relevant clinical treatment.