Self‐Assembly of Amorphous 2D Polymer Nanodiscs with Tuneable Size, pH‐Responsive Degradation and Controlled Drug Release

Amphiphilic bottlebrush block copolymers (BBCs) with tadpole-like, coil-rod architecture can be used to self-assemble into functional polymer nanodiscs directly in water. The hydrophobic segments of the BBC were tuned via the ratio of ethoxy-ethyl glycidyl ether (EE) to tetrahydropyranyl glycidyl ether (TP) within the grafted polymer sidechains. In turn, this variation controlled the sizes, pH-responsiveness, and drug loading capacity of the self-assembled nanodiscs. Notably, as EE exhibited faster hydrolysis than TP, the nanodiscs featured variable degradation rates under mild acidic conditions, aiding small molecule release and time-dependent and complete degradation of discs into fully water-soluble copolymers. The nanodiscs demonstrated biocompatibility and cellular uptake by breast cancer cells, underscoring their potential development into drug delivery systems.