The development of a simple nanoparticle assembly methodology coupled with on-demand disassembly of the self-assembled structures plays an important role in designing smart nanotherapeutics. Our group is developing intelligent boron-based nanomaterials to deliver B-10 with high loading and specificity for boron neutron capture therapy (BNCT). BNCT relies on the homogeneous deposition of high loading of B-10 drug in the solid tumor tissue followed by low energy thermal neutron irradiation to cause lethal damage to the tissue. To achieve a homogeneous distribution of boron drugs in the solid tumor, we present the preparation of a stimuli-responsive polymer-coated BCNO nanoparticle (D~ 5 nm) that self-assembled into 100 nm structures bearing a negative surface charge for optimal tumor accumulation via the EPR effect. Upon entering the tumor microenvironment, the acid-labile linker will disintegrate into individual positively charged BCNO nanoparticles. Herein, we will present the self-assembly of boron nanoparticles via two methods: (1) sequential and (2) single-step functionalization of polymer ligands. Our preliminary results showed that the sequential functionalization resulted in large aggregated structures (D~200-300 nm). In contrast, a single-step functionalization of polyethyleneimine-conjugated polyethylene glycol via a Schiff base bond onto the BCNO nanoparticles resulted in self-assembled structures with the optimal size for tumor accumulation at physiological pH. Upon exposure to acidic pH (6.3), the larger self-assembled structures (~100 nm) disintegrated into smaller assemblies (~50 nm) along with the liberation of ultrafine nanoparticles (5-10 nm). The surface charge potential was also measured to transformed from 13.4 mV to +10.2 mV upon exposure to pH ~6.3, indicating the cleavage of the polyethylene glycol and exposing the positively charged amino moieties. This simple self-assembly approach could potentially be applied towards the self-assembly of other nanotherapeutics with different reactive linkers based on their specific research targets.

Stimuli-responsive self-assembled polymer-coated boron carbon oxynitride as nanotheranostic agent

ACS Fall 2021

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