Tumor-targeting hyaluronic acid/fluorescent carborane complex for boron neutron capture therapy

Abstract

In cancer therapeutics, boron neutron capture therapy (BNCT) requires a platform for selective and efficient ¹⁰B delivery into tumor tissues for a successful treatment. However, the use of carborane, a promising candidate with high boron content and biostability, has significant limitations in the biomedical field due to its poor water-solubility and tumor-selectivity. To overcome these hurdles, we present in this study a fluorescent nano complex, combining fluorescent carborane and sodium hyaluronate for high boron concentration and tumor-selectivity. Tumor cells actively internalized the complex through binding hyaluronan to CD44, overexpressed on the tumor cell surface. Furthermore, the subcellular distribution of this complex could also be detected due to its fluorescent properties. Moreover, after thermal neutron irradiations, the complex produced excellent cytotoxicity, equal to or greater than that of the clinically-used BPA-fructose. Therefore, this novel complex could be potentially more suitable for BNCT than the boron agent.

Keywords: Boron neutron capture therapy; Carborane; Hyaluronic acid; Polysaccharide; Tumor targeting.