Comparative Toxicity, Biodistribution and Excretion of Ultra-Small Gold Nanoclusters with Different Emission Wavelengths.

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.

Construction of Aptamer-siRNA Chimera/PEI/5-FU/Carbon Nanotube/Collagen Membranes for the Treatment of Peritoneal Dissemination of Drug-Resistant Gastric Cancer.

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.

Tumor-associated macrophages increase the proportion of cancer stem cells in lymphoma by secreting pleiotrophin.

Tumor-associated macrophages (TAMs) are closely related to the occurrence and development of lymphoma, but their mechanism is still unclear. Here we collected peripheral blood and lymphoma tissue from patients with diffuse large B lymphoma. Results showed that the proportion of TAMs in high-risk group was significantly higher than that in low-risk group. Moreover, the expressions of pleiotrophin (PTN), PTPRZ1 (PTN receptor) and ß-catenin in lymphoma tissues of high-risk group were also significantly higher than those in low-risk group. Correlation analysis showed that the proportion of TAMs in lymphocyte was positively correlated with the expression of PTN and PTPRZ1 in lymphoma tissue. In vitro experimental results showed that TAM promoted the invasion and proliferation of lymphoma cells by secreting PTN. We also found that TAMs increased the proportion of cancer stem cells in lymphoma. Animal experiments showed that TAMs promoted lymphoma growth. Both Ki-67 proliferation index and CD44+cancer stem cells increased significantly in TAM group. Blocking PTN or ß-catenin partly inhibited these effects of TAMs. In conclusion, TAMs increased the proportion of cancer stem cells through PTN/ß-catenin pathway in lymphoma.

Preparation of anchovy (Engraulis japonicus) protein hydrolysates with high free radical-scavenging activity using endogenous and commercial enzymes.

Anchovy protein hydrolysates with high free radical-scavenging activity were prepared by endogenous and commercial enzymes. Various hydrolytic factors (commercial protease composition, protease concentration, temperature, and reaction time) were optimized. Using a single-factor experiment, three commercial proteases (Protamex, Flavourzyme 500 MG, and Alcalase 2.4 L) were selected for further optimization using a simplex lattice design. The optimum composition of Protamex:Flavourzyme 500 MG:Alcalase 2.4 L was found to be 1.1:1.0:0.9. The hydrolytic conditions (commercial protease concentration, temperature, and reaction time) for the optimum protease composition were optimized using a Box-Behnken design. The optimum hydrolytic conditions were as follows: total commercial protease concentration of 3.27%, pH of 7.5, temperature of 55.4℃, and reaction time of 2.7 h. Under these conditions, hydrolysate with a 1, 1-diphenyl-2-picryhydrazyl scavenging activity of 84.7% was obtained. Meanwhile, a degree of hydrolysis of 33.2% and high protein nitrogen recovery of 87.5% were achieved. The amino acid composition of the hydrolysates demonstrated that they have high nutritional value, thereby suggesting that the hydrolysates have potential to be used as raw material for functional food.