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 10B 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 10B 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, 10B enriched boron carbide (10B4C) nanoparticle is functionalized with polyglycerol (PG), giving 10B4C‐PG with enough dispersibility in a physiological environment. Pharmacokinetic experiments show that 10B4C‐PG fulfills the following three requirements for BNCT; 1) low intrinsic toxicity, 2) 10B in tumor/tumor tissue (wt/wt) ≥ 20 ppm, and 3) 10B concentrations in tumor/blood ≥ 3. In vivo study reveals that neutron irradiation after intravenous administration of 10B4C‐PG suppresses cancer growth significantly and eradicates cancer with the help of near‐infrared light irradiation. A bimodal nanosensitizer consisting simply of 10B4C nanoparticles and polyglycerol (PG) is designed for boron neutron capture and photothermal combined cancer therapies. After intravenous administration of the nanosensitizer to a cancered mouse, neutron and near‐infrared light (photon) are irradiated to the tumor just once to suppress its growth and even eradicate it after a month without any obvious adverse effects.