Hyaluronic acid-decorated carborane-TAT conjugation nanomicelles: A potential boron agent with enhanced selectivity of tumor cellular uptake.

Boron neutron capture therapy (BNCT) has received widespread attention as a new type of radiation therapy. The main problem encountered in BNCT is insufficient tumor cellular uptake of boron agents. In this study, cell-penetrating peptide TAT-conjugated o-carborane was synthesized. The conjugation can self-assemble to form positively charged carborane-TAT micelles, and then adsorb negatively charged hyaluronic acid (HA) to give core-shell structured carborane-TAT@HA micelles. Carborane-TAT@HA micelles exhibits a large amount of boron uptake at the tumor tissue through the enhanced permeability and retention (EPR) effect and the ability of HA to bind to CD44 receptors. Carborane-TAT@HA was wrapped by the HA shell during systemic circulation to avoid non-specific uptake of TAT with normal cells, while tumor microenvironment-responsive shedding of HA shell could expose Carborane-TAT to penetrate the cell membrane into tumor cells. Experiments have proved the enhanced selectivity of tumor cellular uptake of the boron drug, displayed excellent drug delivery potential, and can meet the basic requirements of BNCT.