Rational design, multistep synthesis and in vitro evaluation of poly(glycerol) functionalized nanodiamond conjugated with boron-10 cluster and active targeting moiety for boron neutron capture therapy.

Boron neutron capture therapy (BNCT), advanced cancer treatment utilizing nuclear fission of 10B atom in cancer cells, is attracting increasing attention. As 10B delivery agent, sodium borocaptate (10BSH), has been used in clinical studies along with L-boronophenylalanine. Recently, 10BSH has been conjugated with lipids, polymers or nanoparticles to increase selectivity to and the retentivity in tumor. In this work, we designed the anticancer nanoformulations for BNCT consisting of poly(glycerol) functionalized detonation nanodiamonds (DND-PG) as a hydrophilic nanocarrier, 10BSH as a dense boron-10 source, and phenylboronic acid or RGD peptide as an active targeting moiety. For their conjugation, some hydroxy groups in PG were oxidized to carboxy groups (DND-PG-COOH) to conjugate the active targeting moiety through amide linkage. Some hydroxy groups in DND-PG-COOH were then transformed to azide to conjugate 10BSH through click chemistry. After qualitative and quantitative characterization, the nanodrugs were evaluated in vitro using B16 murine melanoma cells in terms of cell viability and BNCT efficacy. As a result, the nanodrugs with and without the targeting moiety exhibited good anticancer efficacies with slight differences upon thermal neutron irradiation. By TEM observation, 10BSH moiety was found to facilitate the cellular uptake more efficiently than the active targeting moieties.