Abstract
Nanoparticle-based contrast agents and therapeutic drugs are an emerging approach for medical diagnostic and cancer therapy due to their enhanced performance over traditional molecular drugs. However, their bioavailability at the disease site is limited by the complex biology and heterogeneity of cancers. Our research group is currently developing the co-assembly of boron carbon oxynitride (BCNO) nanoparticles within a stimuli-responsive double hydrophilic block copolymers (DHBC) via electrostatic complexation as a potential boron nanodrug to improve the therapeutic efficacy of boron neutron capture therapy (BNCT). Herein, we investigated the co-assembly of BCNO nanoparticles within an acid-labile polyethylene glycol-graft-polyethyleneimine (PEG-g-PEI) DHBC and found that the hydrodynamic size and zeta potential of the BCNO nanoassemblies were tunable by changing the mixing ratios of the BCNO nanoparticles and the DHBC, as well as the size of the charged PEI segment. Specifically, we observed that the hydrodynamic size of the BCNO nanoassemblies initially increased with the volume of DHBC, reached a sharp maximum, then decreased to approximately 150 nm. Furthermore, the hydrodynamic size of the BCNO nanoassemblies increased from 150 nm to 220 nm with an increase in the molecular weight of the charged PEI segment from 1800 g/mole to 270,000 g/mole. We also determined that the BCNO nanoassemblies remained stable at physiological pH for up to 14 days. However, under slightly acidic conditions that mimic the pH environment at the tumor microenvironment and within the endosomes, the BCNO nanoassemblies disassembled into smaller cluster sizes, with a positive surface charge. These results suggest that the pH-responsive DHBC/BCNO nanoparticle complex could potentially deliver a higher loading of B10 to the cancer sites for effective BNCT.