Doxorubicin-conjugated <sup>10</sup>B<sub>4</sub>C nanoparticles: Preparation and application in combined boron neutron capturetherapy/chemotherapy
Kexue tongbao(2021)
Boron neutron capture therapy (BNCT), which is capable of killing cancer cells precisely with α particles and recoiling 7Li nuclei produced by the nuclear fission reaction of thermal neutrons and 10B in the cells, has attracted tremendous attentions in recent years. Delivering sufficient 10B into the cancer cells (> 109/cell) is crucial to successful BNCT. Although considerable effort has been devoted to develop cancer-targeted 10B delivery agents, currently only two boron-containing compounds, i.e., borylphenylalanine (BPA) and sodium mercaptoundecahydro-closo-dodecaborate (BSH) are clinically used in BNCT. On the other hand, combining BNCT with other cancer treatments such as chemotherapy, photodynamic therapy, and immunotherapy can enhance the therapeutic efficacy. Thus, it is highly desired to develop multifunctional 10B delivery agents that enable combination cancer therapy. Boron-containing inorganic nanoparticles such as 10B, 10B4C, and 10BN nanoparticles, containing a large number of boron atoms in a single nanoparticle are promising candidates as 10B delivery agents for BNCT. In addition, these nanoparticles possess low toxicity and good biocompatibility, and are rich in surface chemistry that facilitates further tailoring. For biomedical applications of inorganic nanoparticles, surface modification is essential to increase their aqueous dispersibility and colloidal stability. We have recently developed polyglycerol (PG) grafting as a convenient and effective method for surface modification of inorganic nanoparticles. The PG layer of hyperbranched topology contains many hydroxyl groups on the periphery, which not only largely increase the hydrophilicity of the nanoparticles, but also provide reactive groups for further functionalization through chemical reactions. Through this approach, a wide range of functional moieties including targeting ligands, fluorescent tags, and therapeutic drugs and DNAs have been immobilized on the surface of nanoparticles. Herein, we developed DOX-conjugated 10B4C nanoparticles (10B4C-PG-DOX) for combined BNCT/chemotherapy.