Multifunctional and UV Light-Triggered Degradable Highly Branched Vinyl Polymer for Efficient mRNA Delivery

Vinyl polymers synthesized via radical polymerization of (meth)acrylates are widely used in various biomedical fields. We developed a multifunctional, highly branched vinyl polymer, HPNDN, with ultraviolet (UV) light-triggered degradability for highly efficient mRNA delivery. (2-Nitro-1,3-phenylene) bis(methylene) diacrylate (NPBMDA) was copolymerized with 2-(dimethylamino)ethyl methacrylate (DMAEMA) and 3,3,4,4,5,5,6,6-nonafluorohexyl acrylate (NFHA) by reversible addition-fragmentation chain transfer (RAFT) polymerization followed by end-capping with ethylenediamine (EDA), resulting in HPNDN with a highly branched topological structure, multiple fluorine moieties, and multiple amines. Upon exposure to UV light irradiation, HPNDN degrades within 5 min through the cleavage of the ester groups in the NPBMDA units. Importantly, HPNDN can effectively condense mRNA to form nanosized polyplexes, achieving high transfection efficiency of up to 87.99%, 62.75% and 52.37% in African green monkey kidney (COS-7) cells, human embryonic kidney (293T) cells, and rat schwann (RSC96) cells, respectively, without inducing obvious cytotoxicity.