Chitosan-lactobionic acid-thioctic acid-modified hollow mesoporous silica composite loaded with carborane for boron neutron capture therapy of hepatocellular carcinoma

Nanocarriers have been recognized as an effective strategy for developing novel boron-containing delivery agents for boron neutron capture therapy (BNCT) of refractory tumors. Herein, a chitosan-lactobionic acid-thioctic acid-modified hollow mesoporous silica composite loaded with carborane was prepared to achieve effective treatment of hepatocellular carcinoma by BNCT. Notably, the composite remained stable under physiological conditions and exhibited high selective uptake in liver cancer cells. In the tumor microenvironment, the composite could effectively release carborane into the tumor tissue under the dual stimulation of pH and redox. The composite showed excellent efficacy in BNCT treatment of liver cancer cells. Meanwhile, the composite could exert antioxidant and anti-inflammatory effects to reduce the toxic side effects during BNCT. In tumor-bearing mice, the composite could accumulate in tumor tissue with high selectivity. In addition, the composite could be effectively cleared from the normal tissues and could overcome the inflammatory response generated in vivo by the materials in biological applications. Overall, the composite is a promising boron-containing delivery agent in the treatment of hepatocellular carcinoma by BNCT, and can facilitate the biological applications of the silica-like materials in BNCT. (C) 2022 The Authors. Published by Elsevier Ltd.

Automated summary

Nanocarriers, such as the chitosan-lactobionic acid-thioctic acid-modified hollow mesoporous silica composite described in this study, have shown promise in developing effective boron-containing delivery agents for boron neutron capture therapy (BNCT) of refractory tumors. The composite remained stable under physiological conditions, exhibited high selective uptake in liver cancer cells, and effectively released carborane into the tumor tissue in the tumor microenvironment. It demonstrated excellent efficacy in BNCT treatment of liver cancer cells and also exerted antioxidant and anti-inflammatory effects to reduce toxic side effects. Additionally, the composite showed high selectivity in accumulating in tumor tissue and could overcome inflammatory responses generated in vivo. Overall, this composite material is a promising candidate for BNCT treatment in hepatocellular carcinoma and has potential in the field of silica-like materials in BNCT.