Polyglycerol Functionalized ¹⁰B Enriched Boron Carbide Nanoparticle as an Effective Bimodal Anticancer Nanosensitizer for Boron Neutron Capture and Photothermal Therapies

Boron neutron capture therapy (BNCT) is a non-invasive cancer treatment with little adverse effect utilizing nuclear fission of ¹⁰ B upon neutron irradiation. While neutron source has been developed from a nuclear reactor to a compact accelerator, only two kinds of drugs, boronophenylalanine and sodium borocaptate, have been clinically used for decades despite their low tumor specificity and/or retentivity. To overcome these challenges, various boron-containing nanomaterials, or "nanosensitizers", have been designed based on micelles, (bio)polymers and inorganic nanoparticles. Among them, inorganic nanoparticles such as boron carbide can include a much higher ¹⁰ B content, but successful in vivo applications are very limited. Additionally, recent reports on the photothermal effect of boron carbide are motivating for the addition of another modality of photothermal therapy. In this study, ¹⁰ B enriched boron carbide (¹⁰ B₄ C) nanoparticle is functionalized with polyglycerol (PG), giving ¹⁰ B₄ C-PG with enough dispersibility in a physiological environment. Pharmacokinetic experiments show that ¹⁰ B₄ C-PG fulfills the following three requirements for BNCT; 1) low intrinsic toxicity, 2) ¹⁰ B in tumor/tumor tissue (wt/wt) ≥ 20 ppm, and 3) ¹⁰ B concentrations in tumor/blood ≥ 3. In vivo study reveals that neutron irradiation after intravenous administration of ¹⁰ B₄ C-PG suppresses cancer growth significantly and eradicates cancer with the help of near-infrared light irradiation.