Abstract
Abstract The leverage of synthetic polymer self-assemblies (SPSAs) as biomimetic allostery provides unique opportunities for developing bio-inspired soft species. However, the preparation of these soft species remains a challenge likely due to the synthetic difficulties toward SPSAs having four-level hierarchical structural transitions and the compromised colloidal stability of the self-assembled quaternary structures. Herein, we report self-assembly of topological polymers with hydrophilic multicycles (HMCs) for biomimetic allostery. Specifically, cationic copolymers containing HMCs are prepared via a reliable synthetic approach, whose hierarchical self-assembly affords stabilized nanoparticles that undergo biomimetic allostery into quaternary petalled self-assemblies at an intracellular acidic pH of 5.0. The quaternary petalled self-assemblies lead to a mechanical disruption effect on lysosomes like nanomachines, further resulting in enhanced drug delivery efficiency of an anticancer drug-loaded multicyclic copolymers with a tumor inhibition rate 1.6-fold greater than that of the free drug in a murine 4T1 model. Overall, our work highlights the use of HMCs as biomimetic allostery of SPSAs for enhanced biomedical applications.