Abstract
<p class="Style1" style="text-align:justify; margin-bottom:11px"><span style="font-size:11pt"><span style="text-justify:inter-ideograph"><span style="line-height:107%"><span style="font-family:"Times New Roman",serif"><span style="font-size:12.0pt"><span style="line-height:107%">Boron Neutron Capture Therapy (BNCT), an advanced form of combined chemo- and radiotherapy, offers the unique capability to deliver radiation doses with a significant gradient at the cellular level. A primary obstacle to the wider application of BNCT lies in developing an efficacious boron drug capable of achieving high <sup>10</sup>B loading (10<sup>9</sup> boron-10 atoms per gram of tumor cells), maintaining a high tumor-to-blood (T/B) ratio, and ensuring uniform distribution across solid tumors. Boron-based nanomaterials, such as boron nitride, boron nanoparticles, and boron carbide, have emerged as promising candidates for BNCT, attributed to their high boron content and enhanced tumor-targeting efficiency compared to traditional small-molecule boron drugs. However, the synthesis of boron-based nanoparticles that meet the desired criteria for size, shape, and functional attributes for in vivo application remains challenging. These challenges are principally due to the low reactivity and high melting points of boron precursors, their limited solubility in common solvents, and the propensity for nanoparticle agglomeration. <a name="_Hlk154507800">Herein, we present the synthesis and functionalization of boron carbon oxynitride (BCNO) nanoparticles as a potential theranostic agent. Specifically, we will be presenting a modular methodology in functionalizing BCNO nanoparticles with functional polymers, double hydrophilic block copolymers, and amphiphilic block copolymers. The physicochemical characteristics of these nanoparticles were meticulously analyzed using Transmission Electron Microscopy (TEM), Dynamic Light Scattering (DLS), Thermogravimetric Analysis (TGA), alongside assessments of their in vitro behavior, including cytotoxicity, intracellular uptake, and BNCT-induced tumoricidal effects. To optimize the in vivo stability of BCNO nanoparticles as theranostic agents, we explored various functionalization strategies to maximize polymer grafting density. This investigation includes an evaluation of covalent versus non-covalent conjugation methods, the impact of nanoparticle surface pre-treatment in alkaline media, and the influence of electrostatic functionalization on polymer grafting density and nanoparticle stability in different media. </a></span></span></span></span></span></span></p>