Gene therapy is a modern medical technology for treating various diseases of a genetic origin. However, the lack of high-efficiency gene delivery carriers, especially polymer vectors, significantly hinders its clinical application. Topological structure plays a critical role in the gene delivery of cationic polymers in the development of polymer vectors. In various topologies, cyclic structures are highly attractive due to their unique properties. However, considering the difficulty of synthesis, the polymerisation method significantly affects the obtained cyclic structures. To explore the control of different cyclic structures and their impact on gene therapy, a series of cyclic poly(β-amino ester)s (CPAEs) with different cyclic structures were synthesised by reaction stage dependent cyclisation strategy, and their cyclic structures were confirmed by photoluminescence spectroscopy and nuclear magnetic resonance spectroscopy (NMR). The macro rings proved to be beneficial with trans-gene expression in vitro experiments. In addition, a series of CPAEs with different chemical compositions were synthesised and demonstrated the superiority of macro cyclic polymer vectors in gene therapy compared with their corresponding branched structures. This work achieved the controllable synthesis of different cyclic structures via a first-time proposed reaction stage dependent cyclisation strategy, and provides a new class of high-performance CPAE vectors, which gives essential insights for future studies on the structure-performance relationship of polymer vectors.

Poly(β-amino ester)s cyclic structure control via reaction stage dependent cyclisation strategy for enhanced gene transfection

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