Abstract
A multi-functional mesoporous silica nanoparticle (MSN)-based boron neutron capture therapy (BNCT) agent, designated as T-Gal-B-Cy3@MSN, was synthesized with hydrophobic mesopores for incorporating a large amount of o-carborane (almost 60% (w/w) boron atoms per MSN), and the amines on the external surface were conjugated with trivalent galactosyl ligands and fluorescent dyes for cell targeting and imaging, respectively. The polar and hydrophilic galactosyl ligands enhance the water dispersibility of the BNCT agent and inhibit the possible leakage of o-carborane loaded in the MSN. Confocal microscopic images showed that T-Gal-B-Cy3@MSNs were endocytosed by cells and were then released from lysosomes into the cytoplasm of cells. Moreover, in comparison with the commonly used clinical BNCT agent, sodium borocaptate (BSH), T-Gal-B-Cy3@MSN provides a higher delivery efficiency (over 40-50 fold) of boron atoms and a better effect of BNCT in neutron irradiation experiments. MTT assays show a very low cytotoxicity for T-Gal-B-Cy3@MSN over a 2 h incubation time. The results are promising for the design of multifunctional MSNs as potential BNCT agents for clinical use.
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