o-carborane encapsulated into polymeric micelles for proton boron capture therapy.

Proton boron capture therapy (PBCT), based on proton-boron fusion reactions (11B + p →3α + 8.7 MeV), has the potential to enhance the biological effectiveness of proton therapy. To achieve this potential, the efficient delivery of enough 11B to cancer cells will be paramount. This study demonstrates a newly developed method of poor solvent-mediated spontaneous assembly of polymeric micelles with entrapped o-carborane, in which ethanol is a good solvent for the payload o-carborane but a poor solvent for the hydrophobic segment poly(ε-caprolactone) in this amphiphilic block copolymer. This method provided smaller polymeric micelles compared to use of tetrahydrofuran, a good solvent for the amphiphilic block copolymer, as the sole solvent for both payload and copolymer. The prepared nanoscale formulation enabled the boron-rich cage compound o-carborane to be effectively delivered to tumor cells, and its enhancement of the biological effectiveness of proton therapy was preliminarily validated in a pancreatic ductal adenocarcinoma cell line, MiaPaCa-2, by survival assays and DNA damage assessment. The 111In-labeled congener was also successfully prepared and used in biodistribution assays in normal mice, opening the way to further studies on image-guided PBCT in preclinical animal models.