Self-assembly of cyclic grafted copolymers with rigid rings and their potential as drug nanocarriers

Enhancing the performance of polymer micelles by purposeful regulation of their structures is a challenging topic that receives widespread attention. In this study, we systematically conduct a comparative study between cyclic grafted copolymers with rigid and flexible rings in the self-assembly behavior via dissipative particle dynamics (DPD) simulation. With a focus on the possible stacking ways of rigid rings, we propose the energy-driven packing mechanism of cyclic grafted copolymers with rigid rings. For cyclic grafted copolymers with large ring size (14 and 21-membered rings), rigid rings present a novel channel-layer-combination layout, which is determined by the balance between the potential energy of micelles (E_micelle) and the interaction energy between water and micelles (E_int). Based on this mechanism, we further regulate a series of complex self-assembling structures, including curved rod-like, T-shape, annular and helical micelles. Compared with flexible copolymers, cyclic grafted copolymers with rigid rings provide a larger and loose hydrophobic core and higher structural stability with micelles due to the unique packing way of rigid rings. Therefore, their micelles have a great potential as drug nanocarriers. They possess a better drug loading capacity and disassemble more quickly than flexible counterparts under acidic tumor microenvironment. Furthermore, the endocytosis kinetics of rigid micelles is faster than the flexible counterparts for the adsorption and wrapping process. This study may provide a reasonable idea of structural design for polymer micelles to enhance their performance in biomedical applications.