Expanding Cyclic Topology-Based Biomedical Polymer Panel: Universal Synthesis of Hetero-“8”-Shaped Copolymers and Topological Modulation of Polymer Degradation

8-Shaped copolymers with two macrocycles connected together represent an interesting cyclic topology-derived polymer species due to the simultaneous incorporation of two cyclic moieties and the reported unique physical and chemical properties. To provide a proof-of-concept for a broad readership on biomedical polymers, a well-defined hetero-8-shaped amphiphilic copolymer, cyclic-poly(oligo(ethylene glycol)monomethyl ether methacrylate)- b -cyclic PCL ( c POEGMA- b - c PCL) is synthesized by an elegant integration of intrachain click cyclization and interchain click coupling. The potential of the self-assembled micelles of c POEGMA- b - c PCL for controlled drug release is evaluated by in vitro drug loading and drug release, cellular uptake, cytotoxicity, and degradation studies. Most importantly, the micelles based on c POEGMA- b - c PCL show much slower degradation profiles than the previously reported linear counterpart, POEGMA- b -PCL and tadpole-shaped analog, PEG- b - c PCL because of the presence of cyclic hydrophilic POEGMA segment. Therefore, this study not only develops a robust strategy for a universal precise synthesis of well-defined hetero-8-shaped copolymers based on diverse vinyl and ring-structured monomers, but also reveals the first modulation of polymer degradation property by topological control of the nondegradable moiety in the polymer construct through advanced macromolecular engineering.