Sung Been Lim, Jun Su An, DongHyun Kang, Ha Yeon Park, Mohit J Mehta, Eunyoung Choi, Beob Soo Kim, Hyun Jin Kim
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Synthesis of Amphiphilic Cationic Poly(β-amino acid) Derivatives and Their PEG Length Optimization for mRNA Transfection.
We synthesized a series of amphiphilic cationic poly(ethylene glycol)-b-poly(β-amino acid) derivatives with various lengths of PEG to investigate the effects of PEG lengths on mRNA transfection. The surface charges of the polyplexes with a DPOEG ≥ 4 gradually decreased as DPOEG increased. This indicated that hydrophilic PEG with a DPOEG ≥ 4 was exposed on the surface of the polyplexes, which was further confirmed using 1H NMR. Polyplexes with a DPOEG ≤ 4 exhibited mRNA transfection efficacy similar to that of homopolymers. However, the transfection efficacy of the polyplex with a DPOEG ≥ 12 markedly decreased, mainly because of the decreased cellular uptake and stability of the polyplexes against serum albumin. This indicated that the PEG length considerably affected the delivery efficacy of IVT mRNA. Our results provide useful information for the fundamental polymer design to optimize the PEG length of amphiphilic cationic polymers for systemic IVT mRNA delivery.
期刊介绍：
Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine.
Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.
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