Suppressing Cell Migration through Discoidal Bottlebrush Copolymer Nanocarriers

Precise control over two-dimensional (2D) polymer nanostructures remains a fundamental challenge, as polymer self-assembly overwhelmingly favors spherical morphologies. Here, we introduce a topology-driven design strategy that overcomes this limitation, enabling the predictable and modular formation of amorphous polymer nanodiscs. Our strategy decouples nanodisc diameter from bottlebrush chemistry. By systematically varying the length of hydrophobic poly(ethoxyethyl glycidyl ether) (PEE) side chains in the bottlebrush segment, we obtain precise control over nanodisc diameter while maintaining uniform thickness. This tunability allows investigation of size-dependent cellular interactions using MDA-MB-231 cancer cells. Importantly, we show that nanodiscs can serve as pH-responsive carriers that disassemble under acidic conditions and release ICAM-1 inhibitors (A-205804), resulting in effective suppression of cancer cell migration.