Nanotherapeutics is an emerging and powerful tool in cancer treatment and diagnostic with improved targeting ability, drug solubility, and in achieving a higher therapeutic index with lower side effects. However, their accumulation and fate in the body have raised much concern over the long-term toxicity that arises from the accumulation of nanomaterials in the body. Our group is developing pH-sensitive self-assembled boron carbon oxynitride nanoparticles (D ~ 160 nm) as a potential boron nanodrug for boron neutron capture therapy (BNCT). The engineered boron nanodrug is capable of delivering a high concentration of B-10 to the tumor site and causing lethal damage to the only cancer cell while sparing the neighboring health cell via BNCT. The self-assembly and pH-triggered disassembly nanoparticle system enabled homogeneous distribution of boron drugs in the solid tumor and potentially be eliminated through renal clearance to avoid the potential long-term toxicity arising from nanotherapeutics. Herein, we present the preparation of a stimuli-responsive polymer-coated BCNO nanoparticle (D~ 6 nm) that self-assembled into 160 nm nanostructures 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. The positively charged BCNO nanoparticles not only possessed enhanced cell internalization and diffusional properties throughout the solid tumor for effective BNCT, but could also be eliminated through renal clearance after treatment. We will present our preliminary results on the tumoricidal effect of the ALTS1C1 cell treated with the self-assembled BCNO nanodrug via BNCT.

Assembly and disassembly of Boron nanoparticles in potentiating anti-cancer treatment with minimal toxicity

ACS Spring 2022

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