Self-assembly of amphiphilic nanoparticles as building blocks into hierarchical nanostructures with controllable sizes, morphologies, and functionalities remains a challenging research endeavor. Our group is developing stimuli-responsive boron nanocarrier through the self-assembling of discrete 5 nm BCNO nanoparticles into a ~100 nm boron colloidosome suitable for drug delivery. Upon arriving at the tumor microenvironment, the BCNO colloidsome is designed to disassemble into discrete nanoparticles to enhance the distribution of boron drugs throughout a solid tumor to effectively kill cancer cells without harming neighboring healthy cells via boron neutron capture therapy (BNCT). The as-prepared 5 nm boron carbon oxynitride (BCNO) nanoparticles sequestered within the polyethyleneimine (PEI) segment of a graft copolymer of PEI-graft-(polystyrene/polyethylene glycol) through favorable electrostatic interactions between the negatively charged nanoparticle and the positively charged PEI. The mixed homopolymer brushes are covalently tethered onto the PEI segment via an acid-sensitive Schiff base bond linker. The resulting amphiphilic BCNO nanoparticles self-assembled into 80 – 100 nm superstructures through the self-organization of the patchy BCNO nanoparticles in a selective solvent to minimize the overall free energy. Akin to the self-assembly of amphiphilic block copolymers, the self-assembly of amphiphilic polymers tethered on the surface of the BCNO nanoparticles is also depended on the polymer composition, chain length, and solvent. Increasing the composition of the hydrophobic polystyrene brushes resulted in an increase in the self-assembled structure, consistent with the phase diagram of amphiphilic nanoparticles. Herein we also demonstrated the dual size and surface charge transformation in a slightly acidic environment mimicking the cancer sites.

Self-assembly of stimuli-responsive amphiphilic boron colloidosomes as boron nanodrugs for boron neutron capture therapy

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