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

Abstract

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.