Boron carbon oxy-nitride (BCNO) nanoparticle is a potential new boron drug for boron neutron capture therapy (BNCT) basing on the self-luminescence property and the high payload of boron-10 within a single nanoparticle for maximizing BNCT therapeutic effect. In addition, the surface properties of the BCNO nanoparticles are designed to possess a stimuli-responsive double-hydrophilic block copolymer (DHBP) of polyethylene glycol block polyethyleneimine (PEI-graft-PEG). Previously, we have demonstrated the self-assembly of discrete 6 nm BCNO nanoparticles within the PEI-graft-PEG double-hydrophilic block copolymer. The BCNO nanoparticles induced micellization of the polymer-nanoparticle composites of ~ 160 nm in size that is suitable for tumor accumulation via enhanced permeability and retention (EPR) effect and remained stable at physiological pH. Upon reaching the tumor site, the 160 nm BCNO nanostructures disassembled into 6 nm smaller and positively charged nanoparticles for effective solid tumor penetration. Herein, we are developing a modular methodology in controlling the size of the stimuli-responsive self-assembled BCNO nanostructures. Specifically, we will present our results in modulating the molecular weight of each polymer segment, ratio of polymers, ratio of DHBP to nanoparticles, and the concentration of polymers and nanoparticles. Based on these results, we will propose the self-assembly mechanism of BCNO within PEI-<i>graft</i>-PEG double-hydrophilic block copolymer as a modular method in developing size and charge transformable nanoparticles for biomedical application.

Investigation of the self-assembly of double-hydrophilic polymer coated boron carbon oxy-nitride (BCNO) as a potent boron nanodrug

ACS Spring 2022

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