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 B atom in cancer cells, is attracting increasing attention. As B delivery agent, sodium borocaptate ( BSH, B H SH ⋅ 2Na), has been used in clinical studies along with L-boronophenylalanine. Recently, this boron cluster has been conjugated with lipids, polymers or nanoparticles to increase selectivity to and retentivity in tumor. In this work, anticancer nanoformulations for BNCT are designed, consisting of poly(glycerol) functionalized detonation nanodiamonds (DND-PG) as a hydrophilic nanocarrier, the boron cluster moiety ( B H ) as a dense boron-10 source, and phenylboronic acid or RGD peptide as an active targeting moiety. Some hydroxy groups in PG were oxidized to carboxy groups (DND-PG-COOH) to conjugate the active targeting moiety. Some hydroxy groups in DND-PG-COOH were then transformed to azide to conjugate B H through click chemistry. The nanodrugs were evaluated in vitro using B16 murine melanoma cells in terms of cell viability, BNCT efficacy and cellular uptake. As a result, the B H moiety is found to facilitate cellular uptake probably due to its negative charge. Upon thermal neutron irradiation, the nanodrugs with B H moiety exhibited good anticancer efficacies with slight differences with and without targeting moiety.