Pingge Jiang , Yaxuan Wang , Qiong Wu , Ziyue Wang , Chengfan Wu , Qi Shuai , Yunfeng Yan
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Compared with analogs lacking diselenide bonds, diselenide-containing PBAEs demonstrated robust redox responsiveness and formed PNPs with similar mRNA binding and size, but reduced internal hydrophobicity and improved cellular uptake, mediating potent mRNA delivery. Tail vein injection of diselenide-containing PNPs achieved robust splenic-targeted delivery in mice without helper lipids, unlike the lung-targeted delivery of conventional PBAEs. These findings highlight a novel diselenide-containing PBAE platform for effective mRNA delivery, which has great potential in mRNA-based immunotherapeutic applications.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (72KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>","PeriodicalId":30,"journal":{"name":"Biomacromolecules","volume":"26 7","pages":"Pages 4515-4528"},"PeriodicalIF":5.5000,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Development of Diselenide-Containing Poly(β-amino ester)s for Potent mRNA Delivery to the Spleen\",\"authors\":\"Pingge Jiang , Yaxuan Wang , Qiong Wu , Ziyue Wang , Chengfan Wu , Qi Shuai , Yunfeng Yan\",\"doi\":\"10.1021/acs.biomac.5c00534\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Polymer-based nanocarriers hold promise for nucleic acid delivery, yet the clinical translation of mRNA polymeric carriers remains hindered by insufficient delivery efficiency and cytotoxicity. Here, we synthesized 180 diselenide-containing poly(β-amino ester)s (PBAEs) via Michael addition. In vitro screening identified PBAEs with superior mRNA delivery efficiency, showing that hydrophobic amine backbones with ionizable cationic amine end-capping are critical. The effective mRNA-PBAE polyplex nanoparticles (PNPs) exhibited moderate positive charge, suitable size, potent cellular uptake, and endosomal escape. Compared with analogs lacking diselenide bonds, diselenide-containing PBAEs demonstrated robust redox responsiveness and formed PNPs with similar mRNA binding and size, but reduced internal hydrophobicity and improved cellular uptake, mediating potent mRNA delivery. Tail vein injection of diselenide-containing PNPs achieved robust splenic-targeted delivery in mice without helper lipids, unlike the lung-targeted delivery of conventional PBAEs. These findings highlight a novel diselenide-containing PBAE platform for effective mRNA delivery, which has great potential in mRNA-based immunotherapeutic applications.</div></div><div><div><span><figure><span><img><ol><li><span><span>Download: <span>Download high-res image (72KB)</span></span></span></li><li><span><span>Download: <span>Download full-size image</span></span></span></li></ol></span></figure></span></div></div>\",\"PeriodicalId\":30,\"journal\":{\"name\":\"Biomacromolecules\",\"volume\":\"26 7\",\"pages\":\"Pages 4515-4528\"},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2025-07-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biomacromolecules\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/org/science/article/pii/S152577972500251X\",\"RegionNum\":2,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomacromolecules","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/org/science/article/pii/S152577972500251X","RegionNum":2,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Development of Diselenide-Containing Poly(β-amino ester)s for Potent mRNA Delivery to the Spleen
Polymer-based nanocarriers hold promise for nucleic acid delivery, yet the clinical translation of mRNA polymeric carriers remains hindered by insufficient delivery efficiency and cytotoxicity. Here, we synthesized 180 diselenide-containing poly(β-amino ester)s (PBAEs) via Michael addition. In vitro screening identified PBAEs with superior mRNA delivery efficiency, showing that hydrophobic amine backbones with ionizable cationic amine end-capping are critical. The effective mRNA-PBAE polyplex nanoparticles (PNPs) exhibited moderate positive charge, suitable size, potent cellular uptake, and endosomal escape. Compared with analogs lacking diselenide bonds, diselenide-containing PBAEs demonstrated robust redox responsiveness and formed PNPs with similar mRNA binding and size, but reduced internal hydrophobicity and improved cellular uptake, mediating potent mRNA delivery. Tail vein injection of diselenide-containing PNPs achieved robust splenic-targeted delivery in mice without helper lipids, unlike the lung-targeted delivery of conventional PBAEs. These findings highlight a novel diselenide-containing PBAE platform for effective mRNA delivery, which has great potential in mRNA-based immunotherapeutic applications.
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.